Search PubMed⌕ Search

Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesio-temporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years post-surgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure free for 10 years and one for 15 years after surgery before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗
PubMed1997

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗
PubMed1996

The crystal structure of a five-stranded coiled coil in COMP: a prototype ion channel?

Oligomerization by the formation of alpha-helical bundles is common in many proteins. The crystal structure of a parallel pentameric coiled coil, constituting the oligomerization domain in the cartilage oligomeric matrix protein (COMP), was determined at 2.05 angstroms resolution. The same structure probably occurs in two other extracellular matrix proteins, thrombospondins 3 and 4. Complementary hydrophobic interactions and conserved disulfide bridges between the alpha helices result in a thermostable structure with unusual properties. The long hydrophobic axial pore is filled with water molecules but can also accommodate small apolar groups. An "ion trap" is formed inside the pore by a ring of conserved glutamines, which binds chloride and probably other monatomic anions. The oligomerization domain of COMP has marked similarities with proposed models of the pentameric transmembrane ion channels in phospholamban and the acetylcholine receptor.

Amino Acid Sequence↗
PubMed1996

Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains.

Cluster formation of E-cadherin on the cell surface is believed to be of major importance for cell-cell adhesion. To mimic this process the extracellular part of mouse E-cadherin (ECAD) was recombinantly fused to the assembly domain of rat cartilage oligomeric matrix protein (COMP), resulting in the chimeric protein ECAD-COMP. The COMP domain formed a five-stranded alpha-helical coiled-coil. This enabled the formation of a pentameric ECAD with bundled C-termini and free N-termini. The pentameric protein construct ECAD-COMP and the monomeric ECAD were expressed in human embryonal kidney 293 cells. Electron microscopy, analytical ultracentrifugation, solid phase binding and cell attachment assays revealed that pentamers showed strong self-association and cell attachment, whereas monomers exhibited no activity. At the high internal concentration in the pentamer the N-terminal EC1 domains of two E-cadherin arms interact to form a ring-like structure. Then the paired domains interact with a corresponding pair from another pentamer. None of the four other extracellular domains of E-cadherin is involved in this interaction. Based on these results, an in vivo mechanism is proposed whereby two N-terminal domains of neighbouring E-cadherins at the cell surface first form a pair, which binds with high affinity to a similar complex on another cell. The strong dependence of homophilic interactions on C-terminal clustering points towards a regulation of E-cadherin mediated cell-cell adhesion via lateral association.

Amino Acid Sequence↗
PubMed1996

Interspike intervals during interictal periods in human temporal lobe epilepsy.

We recorded 259 single neurons from mesial temporal lobe structures of 21 patients with complex partial seizures. Interspike intervals within clusters of action potentials (clustered interspike intervals) recorded from cells in mesial temporal structures ipsilateral to seizure initiation were compared to clustered interspike intervals in the contralateral temporal lobe. 'Clusters' were defined as any group of three or more spikes separated by intervals of less than a defined maximum, or two spikes separated by less than half that maximum. The maximum interspike interval which defined a cluster was varied from 5 to 40 ms in 5-ms steps. Significantly smaller proportions of clustered spikes were discharged by neurons in the amygdala, hippocampus and entorhinal cortex from the temporal lobe commonly initiating seizures, compared to neurons in contralateral homotopic regions. When data from the same three structures were combined, significantly fewer cluster interspike intervals between 10 and 25 ms were recorded from cells on the side of seizure onset. Because clustered action potential discharge is a normal pattern of firing for cells that discharge endogenous bursts, the relative decrease in proportions of 10-25 ms clustered interspike intervals occurring in the temporal lobe initiating seizures might reflect a reduction in endogenous burst discharges from that side. Reduced endogenous bursting could be due to the loss of burst discharging neurons as a product of seizure-related excitotoxicity. The identification of decreased interictal single neuronal burst discharge in epileptogenic structures stresses the difference between the interictal and ictal states in patients with complex partial seizures, and the importance of the transition between those states.

Action Potentials↗
PubMed1996

Genetic counselling and testing for susceptibility to breast, ovarian and colon cancer: where are we today?

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.

Breast Neoplasms↗
PubMed1996

Crystallization and preliminary crystallographic study of the pentamerizing domain from cartilage oligomeric matrix protein: a five-stranded alpha-helical bundle.

Cartilage oligomeric matrix protein (COMP) is a pentameric glycoprotein of the thrombospondin family found in cartilage and tendon. Self-association of COMP is achieved through the formation of a five-stranded alpha-helical bundle that involves 64 N-terminal residues (from 20 to 83). The complex is further stabilized by the interchain disulfide bonds between cysteines 68 and 71. We have prepared, by expression in Escherichia coli, several peptides of different lengths from the N-terminal region of COMP and studied their amenability to crystallization. Crystals of the best quality were obtained with a peptide spanning COMP residues 28-72. This peptide forms disulfide linked pentamers with 87% of alpha-helical structure. Crystals were grown by the hanging drop vapor diffusion method, using polyethylene glycol 1500 as a precipitant. The crystals belong to space group P2(1) with unit cell dimensions a = 38.47 angstroms, b = 49.47 angstroms, c = 54.98 angstroms, beta = 103.84 degrees and contain one pentamer per asymmetric unit. They diffract strongly to at least 1.8 angstrom resolution.

Cartilage↗
PubMed1996

[Variation in inspiratory gas flow in pressure support ventilation. The effect on respiratory mechanics and respiratory work].

UNLABELLED: During pressure support ventilation (PSV), the timing of the breathing cycle is mainly controlled by the patient. Therefore, the delivered flow pattern during PSV might be better synchronised with the patient's demands than during volume-assisted ventilation. In several modern ventilators, inspiration is terminated when the inspiratory flow decreases to 25% of the initial peak value. However, this timing algorithm might cause premature inspiration termination if the initial peak flow is high. This could result not only in an increased risk of dyssynchronization between the patient and the ventilator, but also in reduced ventilatory support. On the other hand, a decreased peak flow might inappropriately increase the patient's inspiratory effort. The aim of our study was to evaluate the influence of the variation of the initial peak-flow rate during PSV on respiratory pattern and mechanical work of breathing. PATIENTS: Six patients with chronic obstructive pulmonary disease (COPD) and six patients with no or minor nonobstructive lung pathology (control) were studied during PSV with different inspiratory flow rates by variations of the pressurisation time (Evita I, Drägerwerke, Lübeck, Germany). During the study period all patients were in stable circulatory conditions and in the weaning phase. METHOD: Patients were studied in a 45 degrees semirecumbent position. Using the medium pressurization time (l s) during PSV the inspiratory pressure was individually adjusted to obtain a tidal volume of about 8 ml/kg body weight. Thereafter, measurements were performed during five pressurization times (< 0.1, 0.5, 1, 1.5, 2 s defined as T 0.1, T 0.5, T 1, T 1.5 and T 2) in random order, while maintaining the pressure support setting at the ventilator. Between each measurement steady-state was attained. Positive end-exspiratory pressure (PEEP) and FIO2 were maintained at prestudy levels and remained constant during the study period. Informed consent was obtained from each patient or his next of kin. The study protocol was approved by the ethics committee of our medical faculty. Gas flow was measured at the proximal end of the endotracheal tube with a pneumotachometer (Fleisch no. 2, Fleisch, Lausanne, Switzerland) and a differential pressure transducer. Tracheal pressure (Paw) was determined in the same position with a second differential pressure transducer (Dr. Fenyves & Gut, Basel, Switzerland). Esophageal pressure (Pes) was obtained by a nasogastric balloon-catheter (Mallinckrodt, Argyle, NY, USA) connected to a further differential pressure transducer of the same type as described above. The balloon was positioned 2-3 cm above the dome of the diaphragm. The correct balloon position was verified by an occlusion test as described elsewhere. The data were sampled after A/D conversion with a frequency of 20 Hz and processed on an IBM-compatible PC. Software for data collection and processing was self-programmed using a commercially available software program (Asyst 4.0, Asyst Software Technologies, Rochester, NY, USA). Patient's inspiratory work of breathing Wpi (mJ/l) was calculated from Pes/ volume plots according to the modified Campbell's diagram. Dynamic intrinsic PEEP (PEEPidyn) was obtained from esophageal pressure tracings relative to airway pressure as the deflection in Pes before the initiation of inspiratory flow Patient's additive work of breathing (Wadd) against ventilator system resistance was calculated directly from Paw/V tracings when Paw was lower than the pressure on the compliance curve. Two-way analysis of variance (ANOVA) was used for statistical analysis, followed by post hoc testing of the least significant difference between means for multiple comparisons. Probability values less than 0.05 were considered as significant. RESULTS: COPD patients had significantly higher pressure support than control patients. With decreasing inspiratory flow, Wpi increased significantly in COPD patients.(ABSTRACT TRUNCATED)

Adult↗
PubMed1996

A transient, RCK4-like K+ current in cultured Xenopus olfactory bulb neurons.

A transient K+ current in cultured olfactory bulb neurons of Xenopus tadpoles was studied using the whole-cell patch-clamp technique. The current, which was resistant to 80 mM tetraethylammoniumchloride (TEA) and 10 nM charybdotoxin but blocked by 5 mM 4-aminopyridine (4-AP), activated between -60 and -40 mV and showed time- and voltage-dependent inactivation. Its peak amplitude was nearly independent of the extracellular K+ concentration ([K+]o) in the range of 0.05 to 10 mM, indicating that its conductance increased upon increasing [K+]o. The transient K+ current showed a slow recovery from inactivation with the time for half-maximum recovery from a conditioning pulse to 80 mV for 1 s varying from 100 ms to 500 ms. Complete recovery required as much as 5-10 s at -80 mV, but could be speeded up at hyperpolarized potentials. The current resembles the RCK4 (Kv1.4) current of rat neurons except that its recovery from inactivation was independent of [K+]o. High-frequency stimulation (20-67 Hz) of the neurons with short (5 ms) voltage pulses resulted in a frequency-dependent, progressive inactivation of the transient K+ current. This suggests that, during phasic responses of olfactory bulb neurons, inactivation of the transient K+ current occurs and may lead to lengthening of action potentials and facilitation of synaptic transmission.

Action Potentials↗
PubMed1996

D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures.

The anticonvulsant activity of the novel drug D-23129 (N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester) was evaluated in animal models of epileptic seizures. D-23129 was active after oral and intraperitoneal administration in rats and mice in a range of anticonvulsant tests at nontoxic doses. The compound was active against electrically induced seizures (MES, ED50 rat p.o. = 2.87 mg/kg), against seizures induced chemically by pentylenetetrazole (s.c. PTZ, ED50 mouse p.o. = 13.5 mg/kg), picrotoxin and N-methyl-D-aspartate (NMDA) and in a genetic animal model, the DBA/2 mouse. It was not active against seizures induced by bicuculline and strychnine. Motor impairment, evaluated with the rotarod test and by observation in the open field, was minimal at doses showing anticonvulsant activity. D-23129 was very effective in elevating the threshold for electrically and chemically induced seizures. Considering the dose increasing the MES threshold by 50% (TID50 mouse i.p. = 1.6 mg/kg; TID50 rat i.p. = 0.72 mg/kg) and the TD50 obtained in the rotarod test, the protective index of D-23129 is better than that of valproate and phenytoin. During 14 days chronic oral treatment with 15 mg/kg, no development of tolerance was observed. D-23129 thus presents an orally active, safe, broad spectrum anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used. We expect that D-23129 will improve the treatment of refractory seizures in humans.

Administration, Oral↗
PubMed1996

Effects of chronic morphine pretreatment on amygdaloid kindling development, postictal seizure and suppression and benzodiazepine receptor binding in rats.

Effects of chronic morphine pretreatment on the development of amygdaloid kindling, seizure suppression and benzodiazepine (BDZ) receptor binding in rats were evaluated. The morphine-pretreated animals showed faster acquisition of seizure activity. Further evaluation of the postictal seizure suppression immediately after a fully kindled seizure demonstrated that morphine-pretreated rats had a decreased sensitivity to subsequent kindling stimulations. Twenty-four hours after the last electrical stimulation, saline-pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation site, compared to saline controls. Morphine-pretreated amygdala-kindled rats had significantly higher BDZ binding in piriform, entorhinal and sensorimotor cortices, basolateral and cortical amygdaloid nuclei, dentate gyrus, CAI-3 areas, substantia nigra pars reticulata and periaqueductal gray. The present study indicates that the previous experience with chronic morphine modifies the kindling process and that the enhanced BDZ receptor binding detected in our experiments may be involved in the enhanced postictal seizure suppression observed in these animals.

Amygdala↗
PubMed1996

Chronic and single administration of pentylenetetrazol modifies benzodiazepine receptor-binding: an autoradiographic study.

Benzodiazepine (BDZ) receptor-binding changes in the rat brain induced by pentylenetetrazol (PTZ) were investigated by in vitro autoradiography. Our experiments revealed that a single PTZ administration produced BDZ-binding decrease in cingulate, frontal, temporal, parietal and piriform cortices; caudate putamen; medial, basolateral and cortical amygdaloid nuclei; medial, ventromedial and ventroposterior thalamic nuclei; substantia nigra pars compacta and periaqueductal gray. Fully kindled rats with chronic PTZ treatment showed reduced BDZ receptor-binding in cingulate, frontal, parietal and piriform cortices; caudate putamen; medial, ventromedial and ventroposterior thalamic nuclei; and periaqueductal gray. These effects resulted from decrease in the binding capacity. Our results support that PTZ-induced chemical kindling may be associated with significant changes of the GABAergic systems and BDZ-binding from the first administration.

Animals↗
PubMed1996

Pharmacological studies with cetrorelix (SB-75), a potent antagonist of luteinising hormone-releasing hormone.

The antitumour and hormone-suppressive effects of the luteinising hormone-releasing hormone LH-RH antagonist Cetrorelix (D-20761) and its pamoate salt (D-20762) were investigated in the model of the DMBA-induced mammary carcinoma of female rats and by testosterone determinations in normal male rats. Treatment with single high doses of D-20761 induced a rapid decrease of tumour weights with a dose-dependent duration of action. Strong antitumour effects were also observed by applying different multiple dose schedules, including a initial high dose (3.16 mg/kg, s.c.) followed by a low maintenance dose (31.6 micrograms/kg, s.c.). The stability of the molecule against degrading enzymes led to the idea of using the poorly soluble pamoate salt for facilitating a sustained release of active compound. This salt indeed induced a prolonged suppression of tumour growth and of testosterone levels. In conclusion, we found that Cetrorelix is a highly effective LH-RH antagonist which should be further developed for the treatment of hormone-dependent diseases.

Animals↗
PubMed1996

Introduction to temporal lobe epilepsy.

Epileptic disorders are classified as idiopathic when they are genetically transmitted conditions that consist of epilepsy only, with no structural lesions in the brain and no associated neurological deficits, and symptomatic when they result from some other primary brain lesion or insult. Symptomatic temporal lobe epilepsy can be further divided into mesial temporal lobe epilepsy (MTLE), the condition associated with hippocampal sclerosis; lesional temporal lobe epilepsy due to specific identifiable lesions localized to areas that preferentially project to mesial temporal structures; and cryptogenic temporal lobe epilepsy, for which no etiology can be determined. Intensive clinical and basic research on MTLE, perhaps the most common form of human epilepsy, is currently being carried out in epilepsy research centers, and a number of experimental animals models have been developed to help elucidate the pathophysiology of this condition. Animal models are also important for determining how specific lesions induce epileptogenicity, and whether the neuronal mechanisms in mesial temporal lobe limbic structures are the same as those in neocortex. Cryptogenic temporal lobe epilepsy remains a major clinical challenge, and much more information needs to be derived from research on patients before relevant experimental animal models can be created.

Animals↗
PubMed1996

Pentylenetetrazol-induced kindling: early involvement of excitatory and inhibitory systems.

Alterations in the brain of rats receiving a single non-convulsive administration pentylenetetrazol (PTZ), 30 mig/kg, i.p. (single PTZ group) were investigated and compared with those detected in fully PTZ kindled rats (chronic PTZ group). In vitro receptor autoradiography experiments showed that both single and chronic PTZ groups presented mu opioid and benzodiazepine (BDZ) receptor binding in specific brain areas. Using an antibody generated against the delta opioid receptor (DOR-1), it was found that DOR-1 like immunoreactivity was reduced in cortex and amygdala in mice following single and chronic PTZ administration. Microdialysis experiments revealed that the administration of PTZ 30 mg/kg, i.p. in freely moving rats without previous experience with the drug, induces a rise in glutamate release, detected in the first and second 10 min dialysates collected from amygdala (138% and 50%, respectively) and frontal cortex (70% and 45%, respectively) as well as aspartate in frontal cortex in the first and second PTZ-dialysates (143% and 80%, respectively). Subsequently, values returned to basal conditions. It may be speculated that decreased BDZ receptor binding results from enhanced release of GABA. On the other hand, the decrease of mu receptor binding and DOR-1 immunoreactivity observed after PTZ administration may be the result of enhanced levels of opioid peptides probably released over the kindling procedure. In conclusion, the present study indicates that PTZ-kindling is associated with an imbalance between excitatory and inhibitory systems which is apparent early in the epileptogenic process.

Amygdala↗