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Biomedical subjects

R A Weeks

Publications and source records attributed to R A Weeks.

33 records · Page 2Linked to original sources

Tourette's syndrome: a disorder of cingulate and orbitofrontal function?

We discuss the clinical characteristics of tics and Tourette's syndrome (TS) and also possible treatment options. Based upon an overview of published pathophysiological and PET data, and the results of a recent PET study of changes in opioid receptor binding in TS, we hypothesize that the disease arises due to dysfunction within the cingulate and orbitofrontal cortex. The beneficial effects of dopamine receptor antagonists and dopamine-depleting agents in TS are suggested to be mediated via basal ganglia-thalamofrontal circuits, while opioid agents may act directly on the cingulate.

Cerebral Cortex↗

Blockade of central alpha 2-adrenoceptors enhances the carotid occlusion response in dogs.

Intravertebral artery injection of yohimbine at total doses of 10, 50, 100 and 200 micrograms caused dose-related enhancement of the systemic pressor response to bilateral carotid artery occlusion (BCO) in dogs; the response was depressed by 5000 micrograms yohimbine. Basal blood pressure was increased by 100 and 200 micrograms yohimbine, and decreased by 5000 micrograms. Intravertebral artery injection of rauwolscine, 5 micrograms enhanced the BCO response but had no effect on basal blood pressure. Corynanthine, 200 or 500 micrograms was ineffective. The pressor response to intravenously administered noradrenaline was not affected by any of the drugs. It is concluded that enhancement of the BCO response by yohimbine and rauwolscine is caused by blockade of central alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗

alpha 1- and alpha 2-vascular adrenoceptors in the dog.

Prazosin inhibited contractions of isolated electrically stimulated dog pulmonary artery preincubated with (-)-7-3H-norepinephrine, but had no effect on 3H-overflow, whereas yohimbine enhanced both responses. In pithed dogs the cumulative doses of yohimbine required for 50% inhibition of the pressor effects of clonidine, phenylephrine and norepinephrine were 23, 188 and 35 micrograms/kg i.v., and those for prazosin were 9, 1.5 and 5 micrograms/kg i.v., respectively. The agonists could be ranked in pairs depending on the extent to which the antagonists discriminated members of the pair: clonidine-phenylephrine > phenylephrine-norepinephrine > clonidine-norepinephrine. The results suggest that pressor effects in dogs are mediated by both alpha 1- and alpha 2-vascular (i.e. postsynaptic) adrenoceptors.

Animals↗

Troponin C-like proteins (calmodulins) from mammalian smooth muscle and other tissues.

1. An acidic protein with properties similar to those of troponin C from rabbit skeletal muscle has been shown to be present in bovine and rabbit smooth muscles, chicken gizzard and rabbit liver, kidney and lung. 2. A simple new method involving the use of organic solvents is described for the purification of the troponin C-like proteins from various tissues. 3. The troponin C-like proteins can be distinguished from rabbit skeletal-muscle toponin C by their electrophoretic behaviour on polyacrylamide gels at pH 8.3 in the presence and absence of Ca2+. The troponin C-like proteins have been shown to form complexes with rabbit skeletal-muscle troponin I that migrate on electrophoresis in polyacrylamide gels. 4. Behaviour on electrophoresis, amino acid analysis and the patterns of CNBr digests on polyacrylamide gels indicate that the troponin C-like proteins from bovine uterus and aorta, rabbit uterus, and liver and chicken gizzard are very similar to, if not identical with, bovine brain modulator protein. 5. With bovine cardiac muscle the organic-solvent method yields a preparation consisting of roughly similar amounts of troponin C and troponin C-like protein. 6. By the isotope-dilution technique, troponin C-like protein has been shown to represent 0.42% of the total protein in rabbit uterus. 7. In homogenates of smooth muscle, rabbit lung, kidney and brain, the troponin C-like proteins form a complex with other protein (or proteins) that requires Ca2+ for its formation and that is not dissociated in 9M-urea.

Amino Acids↗

Characterization of a region of the primary sequence of troponin C involved in calcium ion-dependent interaction with troponin I.

1. The CNBr digest of troponin C from rabbit fast skeletal muscle was shown to possess many of the functional properties of the whole troponin C molecule. 2. A peptide corresponding to residues 83-134 was isolated, which forms a Ca(2+-dependent complex with troponin I and neutralizes the inhibition by troponin I of the Mg(2+-stimulated adenosine triphosphatase of desensitized actomyosin. 3. The peptide inhibits the phosphorylation of fast-skeletal-muscle, but not cardiac-muscle, troponin I, by 3' :5'-cyclic AMP-dependent protein kinase. In this property it was as effective as whole skeletal-muscle troponin C when compared on a molar basis. 4. Biological activity was also present in other fractions obtained from the CNBr digest. 5. By gel filtration and affinity chromatography of the whole CNBr digest of troponin C, two peptides, one of which was identified as representing residues 83-134, were shown to form Ca(2+-dependent complexes with troponin I. 6. The significance of these findings for the mechanism of interaction of troponin C and troponin I is discussed.

Adenosine Triphosphatases↗

Prazosin and presynaptic alpha-receptors in the cardioaccelerator nerve of the dog.

In vagotomized, spinal-sectioned dogs, prazosin and phentolamine enhanced positive chronotropic responses to cardiac accelerator nerve stimulation. In additional dogs the inhibition by clonidine of heart rate response to continuous accelerator nerve stimulation (presynaptic effect), and the vasopressor effect of clonidine (post-synaptic effect), were antagonized by prazosin, phentolamine and yohimbine; cumulative doses for 50% antagonism of the cardiac chronotropic effect were 103, 50 and 13 microgram/kg i.v., respectively, and those for 50% antagonism of the vasopressor effect were 39, 38 and 3 microgram/kg i.v., respectively. On isolated rabbit pulmonary artery, prazosin antagonized electrically evoked contractions but had no effect on 3H output, whereas yohimbine enhanced both. The results indicate that prazosin, like phentolamine and yohimbine, blocks presynaptic alpha-adrenergic receptors on the cardiac accelerator nerve of the dog but, unlike yohimbine, prazosin does not block these receptors on noradrenergic nerves of rabbit pulmonary artery. It is concluded that the relative activity of a compound at pre- and postsynaptic alpha-receptors is not the same for all organs. The results are discussed relative to the fact that prazosin causes hypotension without significant reflex tachycardia in dog and man.

Animals↗

Affinity-chromatographic isolation and some properties of troponin C from different muscle types.

1. The formation of a complex between troponin I and troponin C that is stable in 6M-urea and dependent on Ca2+ was demonstrated in extracts of vertebrate striated and smooth muscles. 2. A method using troponin I coupled to Sepharose is described for the rapid isolation of troponin C from striated and smooth muscles of vertebrates. 3. Troponin C of rabbit cardiac muscle differs significantly in amino acid composition from troponin C of skeletal muscle. The primary structures of troponin C of red and white skeletal muscle are very similar. 4. The troponin C-like protein isolated from rabbit uterus muscle has a slightly different amino acid composition, but possess many similar properties to the forms of troponin C isolated from other muscle types. 5. The electrophoretic mobilities of the I-troponin C complexes formed from components isolated from different muscle types are determined by the troponin I component.

Amino Acids↗

Auditory location as an encoding dimension.

In two experiments, subjects were given five successive short-term memory tests. In Experiment 1, recall was not significantly facilitated when memory material in the final test was delivered to the ear opposite to the one that received the memory material in the four preceding tests. In Experiment 2, events were presented from two differentially located speakers rather than through headphones. A shift across speakers on the final test did produce proactive interference release. These findings suggest spatial location as a potential encoding dimension of verbal material.

Adolescent↗