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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 703 records · Page 39Linked to original sources
PubMed1975

Kinetics of binding of bovine trypsin-killikrein inhibitor (K unitz) in which the reactive-site peptide bond Lys-15--Ala-16 is cleaved, to alpha-chymotrypsin and beta-trypsin.

Equilibrium measurements of the binding of reactive-site-cleaved (modified) bovine trypsin-kallikrein inhibitor (Kunitz) to alpha-chymotrypsin and beta-trypsin show a stoichiometric 1:1 association with high binding constants. At least in the case of chymotrypsin much evidence is presented that the reaction with modified inhibitor leads to the same complex as the reaction with virgin inhibitor does. The association rate constant of modified inhibitor with chymotrypsin at pH 7, 22.5 degrees C is 15.8 M-1 S-1. This is about 2 x 10(4) times slower than the binding of virgin inhibitor to that enzyme. In the analogous reaction of modified inhibitor with beta-trypsin, however, the association rate constant (1.2 x 10(4) M-1 s-1 at pH 6.9, 22.5 degrees C) is of about the same order of magnitude as it is in the reaction of virgin inhibitor and trypsin. These and analogous phenomena observed in the reactions of virgin and modified soybean trypsin inhibitor (Kunitz) with alpha-chymotrypsin and beta-trypsin suggest that the specificity of both inhibitors to trypsin is strongly reflected in the association rate constants of the modified forms. The dissociation rate constants of the complexes of trypsin-kallikrein inhibitor with chymotrypsin or with trypsin towards the modified inhibitor are estimated to be unmeasurably slow (half-life times of 45 or 1.5 x 10(4) years, respectively).

Alanine↗
PubMed1975

The effect of cleaving the reactive-site peptide bond Lys-15--Ala-16 on the conformation of bovine trypsin-kallikrein inhibitor (K unitz) as revealed by solvent-perturbation spectra, circular dichroism and fluorescence.

Spectroscopic measurements of virgin bovine trypsin-kallikrein inhibitor and its modified species (in which the reactive-site peptide bond Lys-15--Ala-16 is split) indicate a conformational difference between both proteins. The inhibitor contains four tyrosines but no tryptophan. In the modified inhibitor a tyrosyl blue shift is seen in the difference absorption spectrum of modified against virgin inhibitor. The solvent perturbation spectra show an increase of the fraction of exposed tyrosyls from 0.45 in the virgin inhibitor to 0.59 in the modified form. Comparison of the circular dichroism spectra of the modified and virgin inhibitors reveals a decrease of the mean residue ellipticity in the tyrosine and peptide bond region of the modified inhibitor. In the fluorescence spectra a 50% increase in the quantum yield of the tyrosine fluorescence is observed in the modified inhibitor. All these spectroscopic data support the idea, which is also evidenced by the X-ray crystallographic model, that in the modified inhibitor up to five residues from Ala-16 to Arg-20 gain rotational freedom.

Alanine↗
PubMed1975

Antagonism by d-amphetamine of learning deficits in rats induced by exposure to antipsychotic drugs during early postnatal life.

The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones.

Animals↗
PubMed1975

Antagonism by haloperidol of the L-DOPA-induced disruption of a successive discrimination in the rat.

Male rats were trained to perform a conditioned avoidance response combined with a successive discrimination in a shuttle-box. The administration of L-DOPA, 100 mg/kg i.p., after inhibition of peripheral dopa decarboxylase, disrupts the discrimination but not the acoidance behaviour, whereas the administration of the antipsychotic agent haloperidol (HPD), 0.125 mg/kg i.p., disrupts the avoidance behaviour but not the discrimination. The L-DOPA-induced disruption of the successive discrimination was completely antagonized by 0.25 mg/kg of HPD. The present data show that administration of the antipsychotic agent HPD not only inhibits behaviour but also can improve the behaviour in animals with a disturbed function.

Animals↗
PubMed1975

Antagonism by baclophen of the d-amphetamine-induced disruption of a successive discrimination in the rat.

Male rats were trained to performa conditioned avoidance response combined with a successive discrimination in a shuttle-box. The administration of -amphetamine, 4 mg/kg i.p., caused a disruption of the discriminative but not thee avoidance behavior. Baclophen (beta-[-4-clorophenyl]-psi-aminobutyric acid), a GBA-derivative, given in a dose (4 mg/kg i.p.) that had no effect per se on the behavior in this test situation antagonized the -amphetamine-induced hypermotility. The present findins that baclophen antagonized a biochemically induced abnormal behaviour point to an "antipsychotic" action of baclophen in a successive discrimination avoidance test.

Aminobutyrates↗
PubMed1975

Kinetics of the cooperative association of actin to actin filaments.

The cooperative formation of actin filaments from monomers was followed by light scattering and electron microscopy. The results are well described by a simple model mechanism in which the growth and destruction of filaments occurs by stepwise addition or dissociation of protomers. All steps except the dimerisation step are assumed to have identical rate constants. These were found to be 5 X 10(3) M-1 - sec-1 and 3 X 10(-2) sec-1 for the association and dissociation, respectively (at pH 7.5 and in the presence of 10(-3) M calcium chloride). The equilibrium constant of elongation as obtained from the critical concentration is 1.7 X 10(5) M-1. The corresponding equilibrium constant of dimerisation is about 10 million times smaller (cooperativity parameter sigma = 2 X 10(-7)). This makes the nucleation extremely difficult and cooperativity very high. A best fit of the model to the experimental data is achieved when the destruction of a dimer is much faster than the addition of a third protomer (fast monomer- dimer pre-equilibrium). The size of the nucleus from which propagation becomes faster than dissociation is 3.

Actins↗
PubMed1975

Electrophysiological correlates of pathology and surgical results in temporal lobe epilepsy.

Routine pre-operative EEG studies as well as direct brain recording and stimulation carried out during operations were analysed for 59 patients subjected to a standard unilateral anterior temporal lobectomy for the treatment of epilepsy. All patients in the present series were 16 years old or older at the time of operation, which was invariably carried out under local scalp analgesia only. Electrophysiological findings was correlated with pathological changes noted in the resected temporal lobes, and with the effects of surgery upon seizure activity. Pre-operative EEG data correlated with each of four pathological categories when sphenoidal electrodes and intravenous barbiturate narcosis were emplyed. Thirty of 31 patients with mesial temporal sclerosis demonstrated medial temporal primary spike foci, frequently with independent contralateral and extratemporal secondary foci. In addition, one-third of these patients demonstrated unilateral focal decreased barbiturate-induced fast activity in the corresponding sphenoidal to ear channels. Twelve patients with other specific medial focal lesions (mostly hamartomas) also had medial temporal primary foci, often with independent contralateral secondaries but never with extratemporal foci. Two patients in this group also demonstrated focal decreased fast activity in the appropriate sphenoidal-ear channel. Both of these groups did very well post-operatively with respect to their epilepsy. Five patients with large temporal convexity cicatrices antedating seizures all demonstrated lateral temporal primary spike foci without independent secondary foci or focal decreased fast activity and did not do as well post-operatively as the first two groups. Eleven patients had only non-specific changes in the resected temporal lobe and in general did not benefit from surgery. Various combinations of primary and independent secondary spike foci were seen. Only this group demonstrated diffuse or bifrontal spikes during initial EEG recording, and basal mid-line spikes with intravenous thiopentone. Pecilar sharp notched spike were also very common in this group, but not unique to it. Focal decreases in barbiturate-induced fast activity were not noted.

Adolescent↗