Biomedical subjects

N D Cook

Publications and source records attributed to N D Cook.

At least 37 records · Page 2Linked to original sources

PubMed1990

The cerebral hemispheres and bilateral neural nets.

A high-level cognitive dichotomy ("language and context") is reviewed in relation to empirical findings concerning the functions of the human cerebral hemispheres. We argue that the right hemisphere's involvement in the generation of connotative and contextual information in parallel with the denotative and literal language functions of the left hemisphere provides an important insight into the organization of viable cognitive systems. The role of the corpus callosum in producing the dichotomy is discussed. Finally, the generation of asymmetrical activity in structurally symmetrical, bilateral neural nets is described. The model demonstrates how complementary memory states can be generated in bilateral nets without assuming different modes of information processing, provided that the nets have inhibitory, homotopic connections. Unlike excitatory connections, inhibitory connections are sufficient to generate asymmetric hemispheric activity without postulating intrinsic differences between the cerebral hemispheres.

Brain↗

PubMed1988

Inhibition of galactosyltransferase activity by cacodylate buffer.

Cacodylate buffer, frequently used in the assay of galactosyltransferase, causes inhibition of enzyme purified from human pleural effusion. The inhibition is reflected by an increase in the Km (UDP-galactose) and a decrease in Vmax and cannot be reversed by the addition of 2-mercaptoethanol. It is suggested that alternative buffers be used for the study of the enzyme.

Arsenicals↗

PubMed1988

Separation and partial characterization of two galactosyltransferase isoforms from malignant ascitic fluid.

Galactosyltransferase was isolated from human malignant ascites by ammonium sulphate precipitation, alpha-lactalbumin affinity chromatography and by the removal of contaminating immunoglobulins with protein A chromatography. Two isoforms of galactosyltransferase were separated by DEAE chromatography, and partially characterised by gel filtration, non-denaturing polyacrylamide gel electrophoresis, concanavalin A binding and enzyme kinetics. The two forms isolated were compared with the isoenzymes previously described and the biochemical basis for the difference between the two forms discussed.

Ascitic Fluid↗

PubMed1988

Neural net simulation of the corpus callosum.

The effects of simulated anatomical and physiological parameters were investigated in a "neural net" model, where two neural nets corresponding to two small patches of cerebral cortex were connected by a simulated "corpus callosum." The isolated neural nets have previously been shown to exhibit oscillatory activity similar to the raw EEG. By connecting the nets with fibers which have a specified percentage of inhibition and a specified percentage of homotopicity, the effects of such parameters on the cyclic activity of the nets were studied. It was found that, regardless of the inhibitory-excitatory nature of the simulated corpus callosum, the cyclic activity established in one hemisphere is more readily transferred to the contralateral hemisphere, the greater the percentage of homotopic callosal fibers. Learning was more rapid when the effect of the corpus callosum was primarily excitatory, but learning also took place over inhibitory or mixed callosal tracts. The simulation does not therefore resolve the issue of the predominant physiological effect of the corpus callosum, but does indicate that, given the assumptions of the simulation, "learning" can occur regardless of the percentage of excitatory or inhibitory fibers. It is noteworthy that homotopicity was more important for learning across an inhibitory tract than across an excitatory tract.

Animals↗

PubMed1987

The donor specificity and kinetics of the hydrolysis reaction of gamma-glutamyltransferase.

The donor specificity of the hydrolytic reaction of gamma-glutamyltransferase [5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) has been studied by the use of specifically synthesised gamma-glutamyl substrates. It was found that a wide variety of gamma-glutamylated adducts were hydrolysed by the enzyme. The structure of the adduct was relatively unimportant for donor specificity and the enzyme appears to 'recognise' the gamma-glutamyl portion of the donor molecule. In particular the alpha-amino group and the free proton of the gamma-peptide bond appear to be essential for donor activity. The Vmax of hydrolysis increased proportionally to the electron-withdrawing capacity of the adduct moiety. The rate of formation of gamma-glutamyl-enzyme intermediate was therefore dependent upon the structure of the adduct of the gamma-glutamyl donor. The results suggest that the enzyme shows little specificity beyond that for gamma-glutamyl amides and there is therefore no reason to postulate the presence of a specific glutathione-binding site.

Animals↗

PubMed1987

Animal and human studies of a new 99mTc labelled phosphine-isocyanide complex with possible applications to radionuclide ventriculography.

A new 99mTc-phosphine-isocyanide complex with the general structure [99mTc (DEPE)2(CNR)2]+ has been synthesised and tested in animals and one human. In three animal species (rat, rabbit, dog), the complex is an efficient myocardial imaging agent, while in humans it remains in the blood pool. The complex is 100% protein bound in animals and humans, but whereas in humans it is attached to a 51.5 kdalton protein (probably prealbumin), in rabbits it appears to be bound to a larger macromolecule (M.W. greater than 100 kdalton). The efficiency of the complex for blood pool labelling was tested in a human volunteer and compared with the standard in vivo red cell labelling technique with stannous pyrophosphate. A satisfactory radionuclide angiogram could be performed with less than 370 MBq of the complex. The count rate for the complex (cps/MBq) was 15% higher than that obtained with the labelled red cells and the absence of splenic activity was notable. In humans this complex appears to be an efficient blood pool labelling agent which might be useful for radionuclide ventriculography.

Animals↗

PubMed1986

The simultaneous hydrolysis of glutathione and glutamine by rat kidney gamma-glutamyltransferase.

The simultaneous hydrolysis of L-glutamine and glutathione by rat kidney gamma-glutamyltransferase has been studied. At concentrations of the two substrates giving rates approximating to Vmax, it is shown that glutamine hydrolysis predominates. Under saturating conditions for both substrates, 65% of the glutamic acid produced is derived from glutamine. Using [14C]glutamine it is also shown that at physiological plasma concentrations of glutamine (in excess of 400 microM) and glutathione (20 microM) glutamine hydrolysis is the predominating reaction. We therefore suggest that both glutamine and glutathione are important in vivo donors for gamma-glutamyltransferase.

Animals↗

PubMed1986

Monoclonal antibodies against rat kidney gamma-glutamyl transpeptidase show species and tissue specificity.

Monoclonal antibodies have been raised against rat kidney gamma-glutamyl transpeptidase (GGT). All five antibodies immunoprecipitate enzyme activity from solubilized kidney brush-border membranes, but not from hepatocellular carcinoma membranes. Three of the antibodies react immunohistochemically with brush-border membranes in sections of adult rat kidney, but none of the antibodies cross-react with sections of guinea-pig, mouse or marmoset kidney or with untreated or carcinogen-treated rat liver. The antibodies do not recognize GGT in foetal-rat kidney and react poorly with kidney from 2-year-old rat. They do react with tubules trapped within mesenchymal kidney tumours induced by dimethylnitrosamine, but epithelial tumours, which are GGT-positive (although much less so than normal kidney), are not immunoreactive.

Animals↗

PubMed1986

Demonstration of plasma-membrane adenosine diphosphatase activity in rat lung.

The adenosine diphosphatase (ADPase) activity of rat lung has been investigated. Subcellular fractionation of lung tissue homogenates by sucrose density gradient centrifugation has shown the ADPase activity to be associated with the plasma membrane. ADPase was solubilised from the membranes and fractionated by ammonium sulphate precipitation to separate a specific, low-Km ADPase from non-specific alkaline phosphatase activity. The solubilised ADPase has a Km of 50 microM at pH 7.5 and appears to be distinct from ATPase.

Adenosine Diphosphate↗

PubMed1985

The effect of pH on the transpeptidation and hydrolytic reactions of rat kidney gamma-glutamyltransferase.

The effect of pH upon the transpeptidation and hydrolytic reactions of gamma-glutamyltransferase [5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) have been investigated. It was found that the enzyme was irreversibly inactivated below pH 7.5 or above pH 9.4. Transpeptidation was markedly pH-dependent, while hydrolysis was pH-independent. The pH optimum for transpeptidation was found to vary for different acceptors. The ascending limb of the pH-optimum curve is attributed to the pK of the alpha-amino group of the acceptor, while the descending limb of the pH-optimum curve is attributed to an ionisable group in the active site of the enzyme. These observations provide much information about the interaction of the enzyme with the acceptor: (1) the true acceptor for gamma-glutamyltransferase is the deprotonated form of the amino acid; (2) glycylglycine has a similar acceptor activity to methionine, its apparent higher activity being due to the low pK of the alpha-amino group; (3) the enzyme is reversibly inactivated at higher pH by the deprotonation of a group in the active site which is involved in both binding of acceptor and catalysis of transpeptidation (this group is not involved in the hydrolysis reaction); (4) at pH 8.5, the normal pH for assay, only 47% of the enzyme is active, while at pH 7.4 gamma-glutamyltransferase is 93% in the active form.

Animals↗

PubMed1985

Purification of gamma-glutamyltransferase by phenyl boronate affinity chromatography. Studies on the acceptor specificity of transpeptidation by rat kidney gamma-glutamyltransferase.

gamma-Glutamyltransferase has been purified from rat kidney by a novel procedure using phenyl boronate affinity chromatography. The highly purified enzyme has been studied with respect to acceptor specificity for a number of amino acids, amino acid analogues, dipeptides and tripeptides. The acceptor activity is specific for L-amino acids. The amino acids and the majority of the essential amino acids are poor acceptors while the sulphur-containing amino acids are the best acceptors. The acceptor activity is modulated by the substitution of the amino acid side chain. Substitution of the side chain at the delta, gamma or beta positions results in a proportionally decreasing ability to act as acceptor. The carbonyl moiety of the gamma-carboxy group of the acceptor appears to be essential for acceptor activity, absence of an alpha-carboxy carbonyl group increases the Kappm of the acceptor approximately 100-fold.

Amino Acids↗

PubMed1985

Rapid preparation of highly purified human transferrin.

A rapid, two-step purification for human transferrin using DEAE-Sephacel chromatography followed by phenyl-boronate affinity chromatography is described. The method gives a 70% yield and isolates transferrin of over 97% purity which is hemopexin-free. The remaining protein is due to a single contaminant which may be the glycosylated form of albumin.

Chromatography, Affinity↗

PubMed1985

Enzymatic synthesis of [beta-32P]ADP using adenylate kinase and [gamma-32P]ATP.

An enzymatic method for the synthesis of [beta-32P]ADP from [gamma-32P]ATP is described. This substrate is required for the assay of ADPase and is not commercially available. The method described results in a preparation of [beta-32P]ADP of high purity with a yield of approximately 40% the theoretical obtainable.

Adenosine Diphosphate↗

PubMed1985

The inhibition of plant mitochondrial respiration by the synthetic analog of ubiquinone, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT).

The quinone analog, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT), has been shown to inhibit cyanide-sensitive and cyanide-insensitive respiration in higher plant mitochondria. The inhibition is dependent upon the concentration of mitochondrial protein. The low concentrations of UHDBT required to inhibit the cyanide-sensitive pathway (microM) and the cyanide-insensitive pathway (nM) indicate that UHDBT is acting as a tight-binding inhibitor of ubiquinol oxidation. Inhibition of both pathways was dependent upon pH. It is shown that UHDBT appears to be a less potent inhibitor of cyanide-sensitive NADH oxidation than of cyanide-sensitive succinate oxidation, and that the pH dependence of inhibition of these two pathways differs. The inhibition of NADH and succinate oxidation by the cyanide-insensitive pathway shows similar pH dependences although at a given pH NADH oxidation is more susceptible to inhibition than succinate oxidation.

Cyanides↗

PubMed1984

Purification and characterization of the rotenone-insensitive NADH dehydrogenase of mitochondria from Arum maculatum.

The non-ionic detergent lauryl dimethylamine N-oxide (LDAO) has been used to extract the NADH dehydrogenases of Arum maculatum mitochondria. Affinity chromatography on 5'-ADP-Sepharose 4B was used to separate the rotenone-sensitive (complex I) NADH dehydrogenase from the rotenone-insensitive NADH dehydrogenase. An 18-fold purification of the rotenone-insensitive NADH dehydrogenase was achieved. The enzyme is specific for NADH with optimal activity around pH 7.2. The apparent Km for NADH is 28 microM, with dichloroindophenol as acceptor at pH 7.2. The rotenone-insensitive NADH dehydrogenase appears to be a flavoprotein and no iron-sulphur centres were detected by electron spin resonance spectroscopy.

Chromatography, Affinity↗

PubMed1984

The transmission of information in natural systems.

An isomorphism of information storage and transmission in natural systems is presented. First, a structural and functional dichotomy found in the control centres of the predominant systems in the physical, biological and psychological realms is outlined. The dichotomy of control is shown to allow for an intrinsic balance between the preservation of a system's information, on the one hand, and its alteration and usage, on the other. It is then shown that the mechanisms of communication between the control centre elements are isomorphic among these diverse systems. That is, the transmission of information from one control element to another entails its "double-inversion", which allows for the retrieval of the information in its original form by means of a second transfer process. This mechanism of information transmission leads to novel conclusions concerning the nature of the "brain code".

Animals↗

PubMed1984

Callosal inhibition: the key to the brain code.

A mechanism for interhemispheric communication is proposed based upon the assumption of homotopic callosal inhibition. The implied pattern of cortical activity in each cerebral hemisphere is shown to be the mirror-image and "photographic negative" of the contralateral pattern. Mirror-imagery is a direct consequence of (1) approximate cerebral hemispheric bilateral symmetry and (2) homotopic callosal connections. The photographic negative relationship is a direct consequence of (1) bilaterally symmetrical activation of the cortex via subcortical "attentional" mechanisms and (2) inhibition by a unilaterally established engram of an identical cortical pattern contralaterally. In language generation and understanding, excitation predominantly in the left hemisphere produces on the right inhibition of language-related neurons as well as excitation of all surrounding "contextual" neurons. The suggested dichotomy of verbal and contextual functions of the cerebral hemispheres is shown to be supported by previous findings concerned with cognition in brain-damaged patients. Unlike earlier suggestions of linguistic and paralinguistic specializations in the left and right, the mirror-image negative hypothesis is based upon an explicit physiological process rather than unspecified differences in "information processing."

Animals↗

PubMed1984

Homotopic callosal inhibition.

Previous theories concerning the function of the corpus callosum have included a "topographic" column-to-column excitatory theory and a diffuse "regional" inhibitory theory. Here it is shown that a topographic inhibitory model, in conjunction with a postulate concerning surround inhibition among cortical columns, produces complementary patterns of cortical column firing which, although qualitatively different, do not imply quantitative metabolic asymmetries. The cognitive implications of such homotopic inhibition are discussed.

Cerebral Cortex↗