Search PubMed⌕ Search

Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 631 records · Page 35Linked to original sources

Multisite proteins and randomly coiled polymeric ligands. Chain length dependence of binding constants.

A model mechanism was developed for the binding of a rigid multisite protein with a randomly coiled multivalent ligand. Probabilities of the formation of chain loops between sites located at given distances at the protein were calculated by an extension of the concept of ring closure in coiled chain molecules. Expressions were derived for the dependence of overall equilibrium quantities, such as the binding constant between the protein and the ligand, on intrinsic parameters such as intrinsic binding constants, number of sites at the protein and their distances and on the chain length of the polymeric ligand. A pronounced chain length dependence of the overall binding constant was predicted even at chain lengths much longer than the size of the protein. Such a dependence was previously observed for the enzyme prolyl hydroxylase which acts on polymeric substrates like (ProProGly)n. This so far unexplained feature is quantitatively described by the model mechanism which is believed to be applicable to many other interactions of biological importance.

Enzymes↗

Kinetic studies on the helix-coil transition of fluorescent labeled poly(-L-lysine) by the temperature-jump technique.

Fluorescent dansyl labels were covalently attached to poly (L-lysine) (poly(Lys)) with a degree of polymerization of 300 to 600. The degree of labeling was 0.01 to 0.085 (mol label to mol amino acid residues). From the decay of the anisotropy of fluorescence it was concluded that the labels were highly mobile both in the coiled and helical state. A decrease of fluorescence intensity accompanied the helix-coil transition. Identical pH induced transition curves were measured by circular dichroism and fluorescence. The midpoint of the transition was at pH 10.2. The kinetics of the transition were studied by temperature-jump relaxation using fluorescence detection. A single relaxation phase was observed. The relaxation time tau exhibited a distorted bell shaped dependence on the degree of helicity f with a maximum value tau(max) = 15 micros at f = 0.3 and 20 degrees C. It was independent of polymer concentration and of the degree of labeling. A rate constant of helix propagation kF = 10(7) s(-1) was calculated from tau(max) and published values of the nucleation parameter sigma. The activation energy was 16 kJ mol . The observed rate constant is comparable to that of poly(L-glutamic acid) but two orders of magnitude smaller than that found for polyamino acids with nonionizable side chains.

Journal Article↗

Arthrography as a method of diagnosing tear of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb ("gamekeeper's thumb").

Arthrography of the metacarpo-phalangeal (MP) joint of the thumb was performed on 47 thumbs. The normal arthrographic appearance shows a closed joint space, whereas leakage of contrast material indicates tear of the joint capsule with or without an associated tear of a stabilizing ligament. Arthrographic demonstration of the heads of the adductor pollicis muscle was found to be specific for tear of the ulnar collateral ligament (UCL) of the MP joint, a tear which is commonly responsible for its instability. Arthrography is suggested as a safe and accurate diagnostic examination for the early detection of tears of the UCL of the MP joint.

Adolescent↗

Arthrography as a method of diagnosing soft-tissue injuries of the wrist.

Wrist arthrography was performed in 30 patients suffering from post-traumatic wrist sprain, or whom 15 sustained fractures. A longstanding soft-tissue injury was demonstrated in 70% of the whole group and in 60% of wrist sprains not associated with fracture. Findings include radiocarpal-radionulnar communications (26.6%), radiocarpal-midcarpal communications (36.6%), midcarpal-carpometacarpal communications (30%), radiocarpal-pisotriquetral communications (60%), tendon communications (20%), and lymphatic filling (43.3%).

Adolescent↗

The effect of chronic ethanol administration on central neurotransmitter mechanisms.

Rats were maintained on ad lib food and a forced-intake regimen of ehtanol for up to 270 days. The ethanol treatment induced alterations in the metabolism of central catecholamines seen as increased endogenous concentrations of dopamine concomitantly with decreased concentrations of noradrenaline in the limbic forebrain. The synthesis of catecholamines, measured as the accumulation of dopa following inhibition of aromatic amino acid decarboxylase, was unchanged during chronic ethanol treatment. Local application of dopamine into the nucleus accumbens caused a greater increase in locomotor activity in chronic ethanol rats than in controls thus indicating that chronic ethanol treatment increased the sensitivity at or beyond central dopamine receptors. This phenomenon of functional dopamine receptor supersensitivity was first observed after 5 months of ethanol treatment and lasted for about 4 weeks after cessation of the ethanol treatment. The sensitivity of noradrenergic and cholinergic receptor mechanisms appeared to be unchanged after chronic exposure to ethanol. The effect of the GABAergic drug, gamma-butyrolactone (GBL) on the accumulation of dopa after inhibition of aromatic amino acid decarboxylase was studied in chronic ethanol rats. The enhancement of the dopa formation in dopaminergic neurons induced by GBL was markedly attenuated after chronic ethanol treatment. The gross behavioural depression by GBL was also weakened. This may indicate that chronic ethanol treatment causes subsensitivity of GABA receptors.

4-Butyrolactone↗

The effect of lithium on amphetamine-induced locomotor stimulation.

A behavioural study was performed to investigate how lithium interacts with monoamine mechanisms. Acute lithium pretreatment partially antagonized amphetamine-induced locomotor stimulation in mice. A rather small dose of L-dopa, which had no stimulant effect on locomotor activity of its own, caused a dose-dependent antagonism of the lithium-induced suppression of the amphetamine-induced locomotor stimulation. Additionally, acute lithium pretreatment had no effect on the apomorphine-clonidine-induced locomotor stimulation after elimination of presynaptic activity by means of pretreatment with reserpine and alpha-MT. Our interpretation of these results is that the inhibitory effect on amphetamine-induced locomotor stimulation is likely to be mediated via presynaptic mechanisms (i.e., decreased release of catecholamines or inhibition of catecholamine synthesis or a combination of both mechanisms) and, further, lithium seems to have no effect at or beyond the catecholamine receptors. However, the possibility that lithium may increase the activity in neuronal systems antagonizing the catecholamine neurons cannot be excluded.

Amphetamine↗

Kinetics of the interaction of alpha-chymotrypsin with trypsin kallikrein inhibitor (Kunitz) in which the reactive-site peptide bond Lys-15--Ala-16 is split.

Modified trypsin kallikrein inhibitor (I*), with the reactive-site peptide bond Lys-15--Ala-16 split, reacts with alpha-chymotrypsin (E) via an intermediate X to the stable tetrahedral complex C:E + I in equilibrium X leads to C. Formation X constitutes a fast pre-equilibrium (equilibrium constant Kx = 7 X 10(-5) M, association rate constant kx = 4 X 10(3)M-1s-1) to the slow reaction X leads to C (rate constant kc = 2 X 10(-3) s-1), all values at pH 7.5. No intermediate X is observed when alpha-chymotrypsin reacts with I*-OMe in which the carboxyl group of Lys-15 is esterified by methanol. This observation as well as the different pH dependence of the overall association rate constants in the case of I* and I*-OMe indicate tha formation of X precedes formation of the acyl enzyme in the catalytic pathway. The data are compared to the similar results obtained with beta-trypsin and I* or I*-OMe.

Alanine↗

The cherry-red spot--myoclonus syndrome.

Three young women, 2 of them sisters, were found to have cherry-red spots at the macula when they were children. In 1 patient the spots faded before she was 20 years old. In all 3, incapacitating myoclonus and insidious visual loss developed in adolescence. Their intellect is normal and they have no gargoyle-like features. A variety of lysosomal inclusions were noted in cortical neurons in a biopsy specimen taken from 1 patient in childhood. Liver biopsy fifteen years later revealed mucopolysaccharide-like inclusions in Kupffer cells and hepatocytes. Lipofuscin bodies were abundant in neurons and hepatocytes. The patients excrete sialic acid-containing oligosaccharides not present in normal urine, suggesting a defect in degradation of glycoproteins. The specific enzymatic defect in these patients appears to be a deficiency of lysosomal neuraminidase.

Adolescent↗