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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 667 records · Page 37Linked to original sources
PubMed1977

Association kinetics and binding constants of nucleoside triphosphates with G-actin.

The dissociation of the complex between 1:N6-ethenoadenosine, 5'-triphosphate (xiATP) and G-actin was initiated by dilution to concentrations between 1 micronM and 5 nM and monitored by the fluorescence change of xiATP. The results were quantitatively explained by a two-step mechanism: a reversible dissociation of the actin-nucleotide complex followed by a fast irreversible inactivation of nucleotide-free G-actin. Under normal conditions (0.8 mM CaCl2, pH 8.2,21 degrees C), the rate-limiting step was the dissociation of the nucleotide-G-actin complex. The half-time of the dissociation of xiATP from G-actin was 290 s as compared to only 13 s for the following denaturation step of nucleotide-free actin. 1 mM EDTA highly accelerated the dissociation step and, regardless of its concentration, the complex dissociated quantitatively within 1 min. Addition of Ca2+ within 20 s after EDTA addition induced a re-association of xiATP with nucleotide-free but still native G-actin. This reversal was kinetically resolved by means of a multimixing stopped-flow apparatus. The association rate constant was 6 X 10(6) M-1s-1. From the association and dissociation rate constant, a value of 2.5 X (10(9) M-1 was calculated for the binding constant of xiATP to G-actin. The binding constant of ATP (1.4 X 10(10) M-1) was derived from the relative binding constant of xiATP and ATP as determined by fluorescence titration of xiATP-G-actin with ATP. These binding constants are 10(3)-10(4) times higher than values reported earlier on the basis of more indirect data.

Actins↗
PubMed1977

Behavioral changes after chronic ethanol treatment.

Rats were maintained on ad lib food and a forced-intake regimen of ethanol for up to 270 days. Termination of the long-term ethanol treatment caused two types of withdrawal syncromes. The first, an acute withdrawal syndrome was observed within 12 hr after the discontinuation of the ethanol treatment and was characterized by extreme hyper-excitability. The second, a delayed withdrawal syndrome was characterized by a more coordinated behavioral stimulation and developed first after about 3 days after the discontinuation of the ethanol treatment. Bilateral application of dopamine (DA) into the nucleus accumbens of both chronic ethanol and ethanol rats undergoing withdrawal produced a pronounced increase in coordinated locomotor activity which was 8-10 times higher than that of untreated water control rats. This phenomenon was observed first after 5 months of ethanol treatment and lasted for about 4 weeks after the termination of the treatment. This effect of DA was antagonized by haloperidol indicating a specific effect on DA-receptors. It is concluded that prolonged ethanol administration produces an increased sensitivity of the DA- receptors in the nucleus accumbens and further supports the contention that central catecholamine mechanisms are involved in the mediation of the withdrawal syndrome observed after long-term treatment with ethanol.

Alcoholism↗
PubMed1977

Neurometabolic and behavioural effects of haloperidol in relation to drug levels in serum and brain.

A method has been developed for the quantitative determination of haloperidol in brain and other tissues. Such determinations have been made after acute and chronic administration of haloperidol to Sprague-Dawley rats. Different regions of the brain including the striatum, the limbic forebrain and the cerebellum have been analyzed separately. The haloperidol effects on Dopa formation have been studied in the same tissue samples. The stimulation of prolactin secretion via blockade of hypothalamic dopaminergic mechanisms and behavioural effects of the drug have been evaluated in parallel experiments. The elimination of haloperidol from brain tissue is a multiphasic process. The fourth phase of elimination is the slowest with a half life of 4 days. No strict correlation was found between serum and brain concentrations of haloperidol. Both after acute and chronic administration there exists apparently a saturating dose above which the brain concentration of the drug increases very little. The dose seems to coincide with that beyond which little increase in Dopa formation is observed. A pharmacokinetic analysis suggests an element of saturable binding or transfer of haloperidol to brain tissue. This mechanism is not preferentially localized to areas of brain rich in dopaminergic synapses. A good correlation was found between the haloperidol concentration in the brain on the one hand and its effects on behaviour, on serum prolactin values and on Dopa formation on the other.

Animals↗
PubMed1977

The effect of chronic ethanol treatment on behaviour and central monoamines in the rat.

Rats weaned at 16 days of age were treated with various ethanol concentrations (8--24% w/v) for 270 days. The effect of the chronic ethanol treatment on the growth rate, the diurnal pattern of drinking, the open field activity, and the conditioned avoidance acquisition and retention of the rats were studied. Termination of the chronic ethanol administration caused two types of withdrawal syndromes. The first, an acute withdrawal syndrome was observed within 12 h after the discontinuation of the ethanol treatment and was characterized by extreme hyperexcitability. The second, a delayed withdrawal syndrome was characterized by a more coordinated behavioural stimulation and developed first after about 3 days after the discontinuation of the ethanol treatment. Biochemically, the latter withdrawal syndrome was accompanied by an increased rate of tyrosine hydroxylation (measured as the accumulation of dopa after inhibition of aromatic amino acid decarboxylase) in the striatum and dopamine-rich limbic structures. No differences in the accumulation of 5-hydroxytryptophan were observed. Furthermore, there was an increased level of dopamine concomitant with a decreased level of noradrenaline in the limbic areas during ongoing ethanol treatment. On the 4th day after withdrawal of ethanol the endogenous levels of dopamine and noradrenaline were statistically significantly reduced in the limbic structures. The data of the present study indicate that chronic ethanol administration induces various kinds of behavioural changes and that these changes at least partially are mediated via central catecholamine mechanisms.

Animals↗
PubMed1977

Antagonism by locally applied dopamine into the nucleus accumbens or the corpus striatum of alpha-methyltyrosine-induced disruption of conditioned avoidance behaviour.

Male Sprague-Dawley rats were trained to avoid an electric shock in a two-way shuttle-box. The local application of dopamine into the nucleus accumbens or the corpus striatum was found to antagonize the suppression of conditioned avoidance behaviour induced by systemically administered alpha-methyltyrosine, emphasizing the importance of these dopamine-rich brain structures in mediating conditioned avoidance behaviour.

Animals↗
PubMed1977

Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems.

Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons.

4-Butyrolactone↗
PubMed1977

Open field behavior and gross motor development in offspring of nursing rat mothers given penfluridol.

Nursing rat mothers were injected with penfluridol, a dopamine receptor blocking agent, at Day 1, 3, 5 and 7 after delivery, and their offspring were investigated at 6-18 days of age for various aspects of motor behavior development, and at 4, 8 and 12 weeks of age for open field behavior. No deficits were found in the development of locomotion, air righting, startle response and eye opening. Open field ambulation decreased from an abnormally high level at 4 weeks of age to an abnormally low level at 8 and 12 weeks of age. The ability to habituate to an open field decreased from a normal level at 4 weeks of age to an abnormally low level after 8 weeks of age. The behavior deficits were related to a decreased functional activity of the mesolimbic dopamine neuron system, and the possible relation to a clinical dysfunction among children - minimal brain dysfunction - was discussed.

Age Factors↗
PubMed1977

Dorsal silicone rods in the primary care of war injuries.

During armed combat serious hand injuries are often neglected only to receive the attention they deserve far too late. The authors have employed a vigorous approach to the primary care of severe war injuries to dorsum of the hand introducing silicone rods where extensor tendons have been destroyed and where skin closure is obtained using inguinal skin flaps.

Hand Injuries↗
PubMed1977

A comparison between K-wire and compression screw fixation after arthodesis of the distal interphalangeal joint.

Thirty patients underwent arthrodesis of the distal interphalangeal (DIP) joint for various injuries. Fixation with K-wires was compared to fixation by compression screws. The screw method came to be preferred by us, principally because the immobilization time was significantly less and the patients returned to work more quickly. The success rate of fusion and the time required for it were about the same.

Arthrodesis↗
PubMed1977

Electrophysiological studies in two patients with cherry red spot--myoclonus syndrome.

Two unrelated patients with the cherry red spot--myoclonus syndrome, a rare chronic neuronal storage disorder that begins in childhood with progressive myoclonus, cherry red spots at the macula, and easily controlled seizures, but no dementia, have been investigated electrophysiologically in order to characterize the myoclonic and electroencephalographic features of this syndrome. Phenomenologically, the disease most closely resembles the Ramsay Hunt syndrome, although certain unique features are noted and the patients are not photosensitive. Pathologically and clinically, the disease is related to mucolipidosis type I and atypical cases of GM1 gangliosidosis, and the EEGs obtained from our patients are identical to those seen in mucolipidosis type I. Because of the unusual clinical picture presented in this disease, there should be no difficulty in differentiating it from other more malignant storage disorders and progressive myoclonus epilepsies of childhood. Electrophysiological findings suggest that the myoclonic jerks do not originate cortically, but the specific subcortical generators have not been identified.

Adolescent↗
PubMed1977

Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs.

The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function.

Animals↗
PubMed1977

Effect of hypoxia on monoamine synthesis in brains of developing rats.

Tyrosine and tryptophan hydroxylase activity was studied in the postnatal rat brain in vivo by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan, respectively after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. With increasing age there was a significant increase in the amount of dopa and 5-HTP accumulated in the brain after administration of NSD 1015. After 30 min in a 12% oxygen environment there were significant reductions of tyrosine hydroxylase and tryptophan hydroxylase activity at 1,14 and 28 but not 4 days of postnatal age. Further, the decrease in 5-HTP accumulation was significantly more marked at 14 and 28 days than at 1 day of age. Thus, the oxygen-dependent synthesis of the neurotransmitter 5-hydroxytryptamine seems to be less vulnerable in the early postnatal rat brain.

5-Hydroxytryptophan↗
PubMed1976

Kinetics of dimerization of the variable fragment of the Bence-Jones protein Au.

The dimerization of the variable fragment of the Bence-Jones protein Au was examined in phosphate buffers at pH 6.8-6.9 And ionic strength of 0.1 M or 0.2 M at 20 degrees C. The dimerization constant was about 1 X 10(5) M-1. The reaction enthalpy was positive and the process was entropy driven. The association and dissociation rate constants were 9 X 10(6) M-1 s-1 and 1.5 X 10(2) s-1 respectively. Temperature-jump experiments exhibited the presence of two isomers of the dimer, which are present at equilibrium in a ratio of about 1:1. Isomerization occurred with a half-life of about 0.1 s.

Bence Jones Protein↗