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Biomedical subjects

J Nicholson

Publications and source records attributed to J Nicholson.

At least 91 records · Page 5Linked to original sources

Modulation of the catalytic subunit of cyclic AMP-dependent protein kinase by calmodulin, S-100 protein, parvalbumin and troponin.

The activity of the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK), utilizing type II-S, III-S histone or protamine (free base) as a substrate, was augmented in the presence of regulatory protein including calmodulin, S-100 protein, parvalbumin, or troponin. However, inhibition by calmodulin or S-100 but stimulation by parvalbumin or troponin on this A-PK subunit was observed when II-S histone was replaced by V-S, VI-S, VII-S, or VIII-S histone. In addition, the stimulatory effect of calmodulin or S-100 on this A-PK subunit utilizing III-S histone was greatly diminished when half the dose of III-S was replaced by other histones in a bi-mixed form.

Animals↗

Increased inhibitory action against adenosine 5'-triphosphate in the isolated taenia of the guinea-pig caecum by substitution in the A-ring of 2-phenylisatogen.

1 The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 Substitution in the 4- and 7-positions of the A-ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non-specific smooth muscle relaxants. The compounds also possessed ATP-receptor blocking activity. 3 Substitution in the 5- and 6-positions of the A-ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP-receptor antagonism. 4 In a series of 6-substituted 2-phenylisatogens, 6-methoxy-2-phenylisatogen was the most effective ATP-receptor antagonist. This compound also showed the greatest separation of the desired pharmacological activity (ATP-receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis).

Adenosine Triphosphate↗

Cephalic kinetics of intra-arterially injected lidocaine.

The intravenous injection of 3 mg./kg. of lidocaine into the facial artery resulted in internal carotid artery blood levels between 5 and 7 microgram/ml. 15 seconds thereafter. Internal and external jugular vein blood levels exceeded 30 microgram/ml. at the same time. When the same amount of lidocaine was injected into the facial vein, carotid blood levels were less than 3 microgram/ml., peaking at 30 seconds. Concentrations of the local anesthetics in the jugular vein peaked at 15 seconds, exceeding 35 microgram/ml. The feasibility of local anesthetic drugs reaching the cerebral circulation through a retrograde pathway was indicated, suggesting that this mechanism may be the route for some of the untoward reactions observed after the injection of local anesthetics in the head and neck area.

Animals↗

Complete typing of the HLA region in families. III. Analysis of responses in the primed lymphocyte test (PLT).

LCA, a rapid and efficient computer method to allocate blastogenic responses to positive and negative clusters, is described. The method involves the selection of a partition level for an ordered array of values, such that the resulting two clusters have minimal "within-cluster" variances. Individuals to whom the program assigned the same two HLA-D antigens were MLC-identical (cluster 0) in 50% of the cases. This proportion was lower for HLA-D-identical pairs that typed for Dw4 and/or Dw7, indicating that these antigens are less well defined than the rest. PLTs were less efficient than HTCs in HLA-D typing due to the induction of extra (non-HLA-D determined) responses in the higher cluster.

Computers↗

The multiplication of three different isolates of group B streptococci in pregnant mice.

The ability of three streptococcal isolates of different pathogenicity to multiply in the tissues of pregnant mice was investigated following intravenous injection. The highly pathogenic isolate multiplied most rapidly whilst the isolate of low pathogenicity showed the least rapid growth within the observation period of 24 hours. The greatest concentration of streptococci per gram of tissue was found in the placentae of mice injected with the highly pathogenic and moderately pathogenic isolates when compared with the concentration of livers and spleen. Fetal infection did not occur within 24 hours of intravenous injection of the isolates but retarded fetal growth and infection was demonstrable five days after the injection. The isolate of moderate pathogenicity infected a greater proportion of the fetuses than the isolates of low pathogenicity. It is suggested that the outcome of streptococcal infections by the ability of isolates to multiply in host tissues.

Animals↗

In vitro characterization of Ac-RYYRWK-NH(2), Ac-RYYRIK-NH(2) and [Phe1Psi(CH(2)-NH)Gly2] nociceptin(1-13)NH(2) at rat native and recombinant ORL(1) receptors.

The pharmacology of ORL(1) compounds, [Phe1Psi(CH(2)-NH)Gly2]nociceptin(1-13)NH(2) (F/GNC13), Ac-RYYRIK-NH(2) and Ac-RYYRWK-NH(2) was evaluated at rat ORL(1) receptors in frontal cortex (CTX), transfected chinese hamster ovary (CHO) cells, vas deferens (VD) and anococcygeus (AC). Ranked affinities for the inhibition of [3H]nociceptin binding to CTX and CHO's were: Ac-RYYRWK-NH(2) identical withAc-RYYRIK-NH(2) identical withnociceptin>F/GNC13>Dynorphin A>naloxone. The full agonist, nociceptin stimulated [35S]GTPgammaS binding in CTX (E(max)=174%) and CHO's (E(max)=311%); all other ORL(1) peptides acted as partial agonists with the following rank order for E(max) values: Ac-RYYRWK-NH(2) (96% (CTX), 202% (CHO))>F/GNC13 (44% (CTX), 136% (CHO)) identical withAc-RYYRIK-NH(2) (44% (CTX), 115% (CHO)). Schild analysis generated pA(2) values in CTX of 8.59 (F/GNC13) and 9.13 (Ac-RYYRIK-NH(2)). cAMP production in CHO's was inhibited by 77% (nociceptin), 58% (Ac-RYYRWK-NH(2)), 55% (F/GNC13) and 49% (Ac-RYYRIK-NH(2)). Nociceptin inhibited electrically evoked contractions in isolated tissues by 95% (VD) and 98% (AC); partial inhibition was observed with Ac-RYYRWK-NH(2) (72% (VD), 66% (AC)) and Ac-RYYRIK-NH(2) (54% (VD); 37%(AC)). Ineffective in the VD, F/GNC13 caused a small inhibition in the AC that was reversed at higher concentrations. Schild analysis gave pA(2) affinities of 7.32(VD) and 7.34(AC) for F/GNC13 and 8.69(AC) for Ac-RYYRIK-NH(2).

Animals↗

Smear campaign.

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Female↗