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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 523 records · Page 29Linked to original sources
PubMed1983

Differential effects of insulin on brain monoamine metabolism in rats.

The effect of a subconvulsive dose of insulin, which caused a 70% reduction of plasma glucose levels, on catecholamine and 5-hydroxytryptamine turnover in different brain regions of rats was investigated. The turnover of norepinephrine was found to be increased in the hemispheres and that of 5-hydroxytryptamine was increased in the limbic forebrain and hemispheres, whereas the dopamine turnover was decreased in the striatum and limbic forebrain.

5-Hydroxytryptophan↗
PubMed1983

Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed.

cDNA clones encoding three classes of human actins have been isolated and characterized. The first two classes (gamma and beta, cytoplasmic actins) were obtained from a cDNA library constructed from simian virus 40-transformed human fibroblast mRNA, and the third class (alpha, muscle actin) was obtained from a cDNA library constructed from adult human muscle mRNA. A new approach was developed to enrich for full-length cDNAs. The human fibroblast cDNA plasmid library was linearized with restriction enzymes that did not cut the inserts of interest; it was then size-fractionated on gels, and the chimeric molecules of optimal length were selected for retransformation of bacteria. When the resulting clones were screened for actin-coding sequences it was found that some full-length cDNAs were enriched as much as 50- to 100-fold relative to the original frequency of full-length clones in the total library. Two types of clones were distinguished. One of these clones encodes gamma actin and contains 100 base pairs of 5' untranslated region, the entire protein coding region, and the 3' untranslated region. The second class encodes beta actin, and the longest such clone contains 45 base pairs of 5' untranslated region plus the remainder of the mRNA extending to the polyadenylic acid tail. A third class, obtained from the human muscle cDNA library, encodes alpha actin and contains 100 base pairs of 5' untranslated region, the entire coding region, and the 3' untranslated region. Analysis of the DNA sequences of the 5' end of the clones demonstrated that although beta- and gamma-actin genes start with a methionine codon (MET-Asp-Asp-Asp and MET-Glu-Glu-Glu, respectively), the alpha-actin gene starts with a methionine codon followed by a cysteine codon (MET-CYS-Asp-Glu-Asp-Glu). Since no known actin proteins start with a cysteine, it is likely that post-translational removal of cysteine in addition to methionine accompanies alpha-actin synthesis but not beta- and gamma-actin synthesis. This observation has interesting implications both for actin function and actin gene regulation and evolution.

Actins↗
PubMed1983

Local cerebral metabolism during partial seizures.

Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

Adolescent↗
PubMed1983

Discrimination of different domains in fibronectin on the basis of their stability against urea denaturation.

Circular dichroism spectra, thermal transition profiles and proteolytic susceptibility showed that different regions in the multidomain protein fibronectin exhibit different sensitivity against urea denaturation. A 70-kDa fragment obtained by cathepsin D treatment which comprises the N-terminal part of the fibronectin chains, exhibited in 8M urea a spectrum, at 20 degrees C, identical to that of the native fragment and its thermal unfolding was shifted to lower temperatures by only 10 degrees C. The central portions of the fibronectin chains were remarkably unfolded under the same conditions as clearly demonstrated by the spectra and transition profiles of a cathepsin D-raised 125/140-kDa fragment which originates from this region. When fibronectin or its fragments were exposed to 4 or 8M urea at 4 degrees C and the urea subsequently dialysed off, the spectra and transition curves recorded were very similar to those of the native proteins. Nevertheless, this treatment introduced local conformational changes which resulted in the creation of three new cleavage sites for chymotrypsin. The most prominent one was found to be located in the central part of the middle region and no sites were created in the N-terminal 70-kDa region. In the conjunction with sequence information [Petersen et al. (1983) Proc. Natl. Acad. Sci. USA 80, 137-141] it may be concluded that the disulfide rich domains, made up by regions of internal homology of types I and II in the N-terminal portion of fibronectin, exhibit a remarkable conformational stability, whereas the disulfide free middle region which contains type III domains, is much less stable. Some domains in this region are particularly sensitive to urea denaturation and are irreversibly affected already by 4M urea at 4 degrees C. Therefore, the use of high urea concentrations for the elution of fibronectin from affinity columns may lead to an at least partially irreversible unfolding of some domains and a loss of functions associated with these structural elements.

Chymotrypsin↗
PubMed1983

Shape and stability of fibronectin in solutions of different pH and ionic strength.

At low ionic strength (0.05 M) the sedimentation coefficient of monomeric plasma fibronectin was found to vary from 8S, at pH 3 and 11, to 13.5S at neutral pH. The lower s20,w value indicates a stretched arrangement of the value indicates a stretched arrangement of the two arms of the molecule which was observed in most electron microscopic studies. The higher value is consistent with a still very asymmetric but more condensed shape, which is probably brought about by back-folding and interactions between chain segments of different net charge. A model of this internal association is based on the finding that segments of rather different isoelectric points alternate along the fibronectin chains. A similar pH dependence was observed for a 140-kDa fragment from the middle region of fibronectin which carries segments of low and high isoelectric points at its ends. At high ionic strength (0.35 M) the pH dependence of the sedimentation coefficients was less pronounced and intermediate s20,w values were found. This is expected when both repulsive and attractive interactions are weakened by the electrolyte. It was verified by circular dichroism spectra that the protein was not denatured at pH 3 or 11. Thermal transition curves revealed a destabilization at pH 3 but the thermal denaturation occurred well above 20 degrees C at which the pH dependence of the solution shape was studied.

Drug Stability↗
PubMed1983

Therapeutic potentials of centrally acting dopamine and alpha 2-adrenoreceptor agonists.

The antiparkinsonian activity of several dopamine agonists was investigated in an animal model and clinically in parkinsonian patients. The semisynthetic ergoline, pergolide, the partial ergoline, LY 141865 and the 8-alpha-aminoergoline, CU 32-085 were found to be effective antitremor agents in monkeys with ventromedial tegmental lesions. The administration of pergolide or LY 141865 results in a relief of tremor with a concomitant occurrence of severe abnormal involuntary movements, while the administration of CU 32-085 results in a relief of tremor with the occurrence of only minor abnormal involuntary movements. Clinical studies have revealed that pergolide is an effective drug in patients with advanced Parkinson's disease, and it reduces the "on-off" phenomena. The possible regulation of dopamine neurotransmission by the norepinephrine neuronal systems was reviewed. Preliminary data suggest that clonidine may interact with presynaptic dopamine receptors.

Adrenergic alpha-Agonists↗
PubMed1983

[Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy].

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.

Antineoplastic Agents↗
PubMed1983

Heparin-stimulated modification of C1-inhibitor by subcomponent C1s of human complement.

C1-inhibitor and C1s form a very stable complex which migrates with an apparent molecular mass of 180 kDa in dodecyl sulfate gel electrophoresis. A small fraction of the inhibitor (100 kDa) was found to be converted to a large (95 kDa) and a small (2 to 5 kDa) fragment during this reaction. It is concluded that C1-inhibitor is modified by C1s in a similar way as are the related plasma inhibitors alpha 1-proteinase inhibitor, antithrombin III and antiplasmin by their specific proteinases. The fraction of modified C1-inhibitor increased when heparin was present during complex formation. This reaction was complete after 15 s and is comparable with the fast heparin induced formation of modified antithrombin III. Treatment with hydroxylamine led to a complete dissociation of the inhibitor-enzyme complex by dodecyl sulfate. The large inhibitor fragment (and not unmodified inhibitor as reported by other authors) was released.

Complement Activating Enzymes↗
PubMed1983

Histo-mechanical aspects of carpal tunnel syndrome.

Carpal tunnel syndrome is a result of median nerve compression within the carpal canal. Factors associated with the appearance of carpal tunnel syndrome can be related to the bony architecture of the carpal canal, to its contents and to systemic disease. The purpose of this work is to see if changes in the elasticity of the transverse carpal ligament may cause carpal tunnel syndrome.

Adult↗
PubMed1983

Synthesis of orally active cardiosteroid derivatives.

Starting from hellebrigenin, orally cardiotonic active acylcardiosteroid derivatives have been synthesized. D 12316 (acrihellin), the hellebrigenin-3 beta-dimethylacrylate, has been chosen for clinical evaluation.

Animals↗
PubMed1983

Walking cane designed to assist partial weight bearing.

The device described indicates accurately the amount of weight borne on an affected leg. This device consists of two major elements: a weight measuring system incorporated in the walking cane's body, and a feedback mechanism situated in the cane's handle. By means of vibration or lights the patient and the therapist can determine whether or not the affected leg is bearing the prescribed weight. Thirty patients (10 with fractures, 10 with vascular disorders, and 10 below-knee amputees) and 10 healthy people participated in the study. The study concluded that young patients used the feedback information more readily than older patients. The intention in designing such a device is to help orthopedically disabled patients during their convalescence, to minimize strain on ischemic legs, and to assist amputees in monitoring weight-bearing postoperative walking.

Adolescent↗
PubMed1982

Neuromagnetic localization of epileptiform spike activity in the human brain.

Local paroxysmal discharges of epileptic tissue within the human brain, which may be electrically recorded as voltage spikes in the electroencephalogram, also generate extracranial magnetic fields. These fields were assessed by means of recently developed neuromagnetometric techniques. Surface measurements of magnetic spike field strength in the region of the focus appear sufficient to establish the location, depth, orientation, and polarity of currents underlying the paroxysmal discharge.

Brain↗
PubMed1982

Behavioral and electrographic effects of opioids on kindled seizures in rats.

Our laboratory previously suggested that opioid peptides are released by an amygdaloid kindled seizure and may affect the elicitation of a subsequent seizure. The present study examined the effects of morphine, naloxone, enkephalin analogues, and conditions of morphine tolerance and withdrawal on the severity and duration of a series of amygdaloid kindled seizures. The results suggest two distinct opiate/opioid actions on seizures. The first is an anticonvulsant effect on the behavioral manifestations of seizures. This effect is seen following a high dose (50 mg/kg) of morphine or a low dose (6 mg/kg) of enkephalin analogue (LY146104), and is reversed by naloxone. The second is a naloxone-reversible prolonging effect of the high dose of morphine on the electrographic components of the seizures. Receptor affinities of these various opiate/opioid drugs suggest that these two actions are mediated by different receptors which appear not to include high affinity mu receptors.

Animals↗