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M Randić

Publications and source records attributed to M Randić.

At least 73 records · Page 4Linked to original sources
PubMed1977

Responses of identified spinal neurones to acetylcholine applied by micro-electrophoresis.

1. The responses of identified cells in the cat Clarke's column and dorsal horn to micro-electrophoretically applied cholinomimetics and anti-cholinergic substances have been investigated. 2. Both antidromically identified (DSCT neurones) and synaptically activated neurones from the region of the Clarke's column of the spinal cord were excited by ACh. However, the proportion of ACh excited cells was greater in units synaptically activated by ipsilateral dorsolateral funiculus stimulation (78%) than in DSCT neurones (50%). In addition, about 55% of neurones activated either antidromically or synaptically by ipsilateral dorsal column stimulation were excited by ACh. 3. In contrast to a relatively weak excitatory potency on the DSCT neurones (maximum firing frequency did not exceed 130% of the control activated by ipsilateral dorsolateral funiculus stimulation (maximum firing frequency reached 430% of the control level). 4. ACh has a relatively quick and rapidly reversible excitatory effect on Clarke's column neurones and some types of dorsal horn interneurones, which can be obtained also with nicotine. However, the action of nicotine is frequently delayed in onset and recovery. This excitatory action of ACh can be blocked or markedly depressed by dihydro-beta-erythroidine. These results and those obtained with acetyl-beta-methylcholine and atropine seem to suggest that the receptors mediating excitation of the cholinoceptive spinal cells activated either antidromically or synaptically by ipsilateral dorsolateral funiculus stimulation besides predominantly nicotinic have also weak muscarinic properties. 5. Desensitization with repeated applications of ACh and nicotine has been observed in both DSCT neurones and units antidromically activated by ipsilateral dorsal column stimulation. 6. About 11% of units antidromically activated by ipsilateral dorsolateral funiculus stimulation were depressed by ACh. In addition, the depressant effect of ACh was more frequently encountered in the cells unresponsive either to the dorsolateral funiculus or dorsal column stimulation. ACh depression was also seen in units activated either antidromically or synaptically by ipsilateral dorsal column stimulation. In contrast, none of the units synaptically activated by the ipsilateral dorsolateral funiculus stimulation were depressed by ACh. The same was true for spinal neurones receiving convergent peripheral inputs activated either antidromically or synaptically by ipsilateral dorsolateral or dorsal column stimulation. 7. The findings that ACh depression of all tested DSCT neurones is blocked by atropine and readily evoked by acetyl-beta-methylcholine indicates that receptors mediating the effect are of muscarinic type.

Acetylcholine↗
PubMed1976

Molecular connectivity V: connectivity series concept applied to density.

The concept of the expanded series of the connectivity index, chi, is introduced and applied to a consideration of the density of three classes of molecules. Correlations are found using two terms in the expanded series. A preliminary reflection on the extended series terms is made. It is noted that the regression equation constant in the three studies is close to the phase volume, 0.7402, and the possible significance of this fact is discussed.

Alcohols↗
PubMed1973

Sensory inputs to neurones in Clarke's column from muscle, cutaneous and joint receptors.

1. Discharge of neurones at the region of Clarke's column of the cat was recorded intracellularly or extracellularly in response to electrical stimulation of various hind limb nerves or to adequate stimuli applied to a variety of sensory receptors.2. According to the type of excitatory sensory input, the neurones were classified into four groups. Their relative proportions were: muscle group, 55-65%; cutaneous group, 15-25%; joint group, 5-15%; convergent group, 10-20%.3. The location of the neurone cell bodies was examined by marking the site of extracellular recording with fast green. The neurones of the muscle or cutaneous group were found to be within Clarke's column. One out of four neurones tested for the joint group and two out of six cells examined for the convergent group were found to be located outside the column.4. There was no difference in axonal conduction velocity among the neurones of different groups.5. The neurones of different groups could be distinguished in terms of the pattern of discharges recorded under ;resting' conditions and during activation of sensory receptors. It is suggested that information carried by dorsal spinocerebellar tract neurones to the cerebellum has a lower signal-to-noise ratio for cutaneous inputs than for muscle or joint inputs.

Animals↗
PubMed1973

Synaptic action on Clarke's column neurones in relation to afferent terminal size.

1. Excitatory post-synaptic potentials (e.p.s.p.s) were recorded intracellularly from Clarke's column neurones (DSCT neurones) of the cat in response to adequate stimuli applied to a variety of sensory receptors.2. The amplitude of e.p.s.p.s so produced varied from less than 0.2 mV to more than 2-3 mV. The amplitude distribution of e.p.s.p.s suggested that the mean number of ;quanta' of transmitter released by one impulse varied widely from one fibre to another arising from a given type of sensory receptor.3. The average amplitude of e.p.s.p.s evoked by single afferent impulses was significantly smaller for cutaneous inputs than for muscle or joint inputs. However, synaptic action on DSCT neurones produced by different sensory inputs was equally greater, on the average, than that on spinal motoneurones.4. Both small and large e.p.s.p.s in DSCT neurones failed to increase in amplitude during post-synaptic hyperpolarization applied through the cell body. This failure could not be attributed to possible anomalous rectification in the post-synaptic membrane.5. Small and large e.p.s.p.s were comparable in half-decay time, but there was a positive correlation between amplitude and time-to-peak of e.p.s.p.s. It is suggested that the locations of synapses responsible for small and large e.p.s.p.s are intermingled on the dendrites and that large e.p.s.p.s are associated with a longer duration of transmitter action than small e.p.s.p.s.6. Degenerating terminals of primary afferent fibres on DSCT neurones and motoneurones were examined with the electron microscope after chronic section of the dorsal roots.7. Dendritic degenerating terminals showed no significant difference in size between motoneurones and DSCT neurones. Degenerating ;giant' terminals were found on DSCT neurones, but they were located only on or very close to the cell body.8. It is concluded that the major factor responsible for a large number of ;quanta' of transmitter released at synapses on DSCT neurones is the number of multiple synaptic contacts formed by one afferent fibre rather than the size of individual synapses.

Animals↗
PubMed1970

Some factors influencing the release of 5-hydroxyindol-3-ylacetic acid in the forebrain.

1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence either the forebrain content of 5-HIAA or the efflux of 5-HIAA from the cerebral cortex.3. Probenecid (200 mg/kg) caused a twofold increase in 5-HIAA content of the rat's forebrain, while the efflux of 5-HIAA from the cerebral cortex remained unchanged.4. Stimulation of the mid-brain raphé in animals pretreated with probenecid does not produce the rise in the forebrain levels of 5-HIAA seen in stimulated untreated controls and does not affect the efflux of 5-HIAA from the cerebral cortex.5. In preliminary experiments, lysergic acid diethylamide (LSD 25) substantially reduced and/or prevented the increase in the release of 5-HIAA in the forebrain observed in untreated animals with raphé stimulation.

Adrenalectomy↗
PubMed1966

An inhibitory process in the cerebral cortex.

1. In cats, rabbits and monkeys, single cortical shocks can reduce the excitability of cortical neurones for 100-300 msec; the inhibitory effect is readily demonstrated, even in previously quiescent cells, against a background of activity evoked with small amounts of L-glutamate, released from an extracellular recording micropipette by iontophoresis.2. Other forms of cortical activity are also inhibited in a similar way by direct or indirect cortical stimulation; they include single unit discharges produced by iontophoretic applications of ACh or by a cathodal current, spontaneous discharges, and slow wave activity, both spontaneous and evoked.3. Most stimuli which elicit cortical activity also evoke some inhibition in the cortex, for instance, transcallosal volleys, and thalamic or peripheral shocks. In each case, a characteristic, prolonged depression is produced by single shocks.4. The most effective stimuli are direct cortical shocks, especially when applied within the cortex, below a depth of 0.6 mm; surface cathodal shocks are more effective than anodal shocks. These stimuli do not first excite the cells which are inhibited and they are not strong enough to cause appreciable local injury.5. Because of its long duration, the inhibition is often readily maintained by repetitive stimulation at frequencies of 5-7/sec. A cumulative effect leads to a further silent period after the end of stimulation; this increases with the strength, frequency and duration of the tetanus, so that after stimulation at 50-100/sec, the silent period may last for over 1 min. During this time, a stronger depolarizing stimulus can initiate firing.6. The inhibitory effect is often preceded and followed by phases of increased excitability; these may also show cumulative enhancement during repetitive stimulation, and a high frequency tetanus often leads to a short after-discharge, which is then followed by a long silent period, as above. Comparable changes take place in rabbits during spreading depression.7. The inhibitory effect of a direct shock can spread over an area covering 1 cm of cortical surface, affecting the cells through all cortical layers; but the spread is uneven in different directions, being particularly poor under most sulci.8. This type of inhibition can be elicited in all areas of the neocortex, and it is evident in kittens within a week of birth.9. Antidromic pyramidal stimulation is very much less effective in evoking inhibition of Betz cells, and other cortical neurones, than direct cortical stimulation; the inhibition by direct shocks is therefore not likely to be mediated through pyramidal excitation.

Acetylcholine↗
PubMed1966

Nature of a cortical inhibitory process.

1. Since the inhibitory effect of direct or indirect cortical stimulation on cortical units can be overcome by excitation with even more L-glutamate, it is not likely to be due to an excessive depolarization.2. Further evidence that surface stimulation has a hyperpolarizing action on cortical cells was obtained by intracellular recording from over 120 pericruciate cells. Inhibitory post-synaptic potentials (IPSPs) are seen in most cells, which are comparable in threshold and duration with the inhibitory effect observed extracellularly. The IPSPs are usually not preceded by a discharge of the same cells.3. The extracellular slow wave corresponding to the inhibitory effect varies considerably with different preparations and different depths within the cortex. A predominantly positive wave is only seen occasionally. In general, the relevant wave recorded deep in the cortex tends to be mainly negative.4. This negative slow wave can be much potentiated by tetanic stimulation, or, especially, by a large local release of L-glutamate; the last procedure is most effective either very near the surface, or below a depth of 1.0 mm. These observations suggest that inhibitory synapses occur more profusely in the superficial half of the grey matter.5. Unlike L-glutamate, GABA tends to depress the ;inhibitory' slow wave.6. The inhibitory effect must be produced by intracortical neurones, since it is fully preserved in isolated cortical slabs. In both acute and chronic slabs, the inhibition is particularly well marked and long lasting, partly because spontaneous activity and the usual post-inhibitory rebound of excitability are absent.7. The intracortical pathways responsible for the spread of inhibition cannot be situated mainly in the superficial layers, as they are not readily blocked by surface cooling or the application of local anaesthetics.8. One can record unit discharges immediately after a surface shock. Some of these discharges could be from inhibitory interneurones, but they do not last more than 10-20 msec.9. We conclude from the observations described in this and a previous paper (Krnjević, Randić & Straughan, 1966a) that a widespread system of intracortical interneurones can be activated by direct or indirect stimulation of the cortex; these interneurones have a powerful and prolonged inhibitory action on most cortical cells.10. The identity and distribution of the postulated inhibitory interneurones is discussed in the light of some relevant morphological evidence.

Aminobutyrates↗
PubMed1966

Pharmacology of cortical inhibition.

1. We have studied the effects of various pharmacological agents on the cortical inhibitory process described in the previous two papers (Krnjević, Randić & Straughan, 1966a, b); the drugs were mostly administered directly by iontophoresis from micropipettes and by systemic injection (I.V.).2. Strychnine given by iontophoresis or by the application of a strong solution to the cortical surface potentiated excitatory effects, but very large iontophoretic doses also depressed neuronal firing. Subconvulsive and even convulsive systemic doses had little or no effect at the cortical level. There was no evidence, with any method of application, that strychnine directly interferes with the inhibitory process.3. Tetanus toxin, obtained from two different sources and injected into the cortex 12-48 hr previously, also failed to block cortical inhibition selectively. As with strychnine, there was some evidence of increased responses to excitatory inputs.4. Other convulsant drugs which failed to block cortical inhibition included picrotoxin, pentamethylene tetrazole, thiosemicarbazide, longchain omega-amino acids and morphine.5. The inhibition was not obviously affected by cholinomimetic agents or by antagonists of ACh.6. alpha- and beta-antagonists of adrenergic transmission were also ineffective.7. Cortical inhibition was fully developed in the presence of several general anaesthetics, including ether, Dial, pentobarbitone, Mg and chloralose. A temporary reduction in inhibition which is sometimes observed after systemic doses of pentobarbitone, is probably secondary to a fall in blood pressure.8. Several central excitants such as amphetamine, caffeine and lobeline also failed to show any specific antagonistic action on cortical inhibition.9. In view of the possibility that GABA is the chemical agent mediating cortical inhibition, an attempt was made to find a selective antagonist of its depressant action on cortical neurones. None of the agents listed above, nor any other of the substances tested, were able to block this action.10. It was concluded that cortical inhibition differs from spinal inhibition in its pharmacological properties; and that our observations are consistent with the possibility that GABA is the cortical inhibitory transmitter.

Alkaloids↗
PubMedDate not supplied

On 3-D graphical representation of DNA primary sequences and their numerical characterization.

In this article we (1) outline the construction of a 3-D "graphical" representation of DNA primary sequences, illustrated on a portion of the human beta globin gene; (2) describe a particular scheme that transforms the above 3-D spatial representation of DNA into a numerical matrix representation; (3) illustrate construction of matrix invariants for DNA sequences; and (4) suggest a data reduction based on statistical analysis of matrix invariants generated for DNA. Each of the four contributions represents a novel development that we hope will facilitate comparative studies of DNA and open new directions for representation and characterization of DNA primary sequences.

Base Sequence↗
PubMedDate not supplied

On interpretation of well-known topological indices.

Many topological indices lack an interpretation in terms of simple physicochemical quantities. We have reexamined the structural interpretation of well-known topological indices: the connectivity index (1)chi, the Wiener index W, and the Hosoya topological index Z. We relate the success of various indices in structure-property studies to the degree to which they differentiate contributions from more exposed terminal bonds and more buried interior bonds. When considering bond additive properties of alkanes we find better regressions when greater weights are assigned to terminal CC bonds and lesser weights to internal CC. We suggest here that topological indices be discussed in terms of their partitioning into bond contributions, which for different indices and different bonds will assume different values. With this insight we modified the Wiener index W into a new index W, in which bond contributions are determined using the reciprocal of the product of the number of atoms on each side of a bond. Similarly we modified the Hosoya index Z into Z in which the frequency of occurrence of individual CC bonds in the patterns of disjoint bonds are considered. Novel indices are compared with other indices and they show to yield better regressions for boiling points of octane isomers. This suggests a useful classification of topological indices based on the relative magnitudes of the contributions of terminal and interior bonds. To extend such considerations to other indices one needs to consider partitioning of global molecular indices into bond additive terms. A general scheme for partitioning of molecular descriptors into bond contributions is outlined for indices derived from a selection of matrices associated with molecular graphs.

Journal Article↗
PubMedDate not supplied

Characterization of DNA primary sequences based on the average distances between bases.

We outline numerical characterization of DNA primary sequence based on calculation of the average distance between pairs of nucleic acid bases. This leads to a representation of DNA by a condensed 4 x 4 symmetrical matrix, the elements of which give the average separation between pair of bases X, Y in DNA (X, Y = A, C, G, T). As an invariant of choice we consider the leading eigenvalue of the derived 4 x 4 matrix. Additional structurally related invariants were obtained by constructing additional "higher order" 4 x 4 matrices derived from the initial 4 x 4 matrix by raising its elements to higher powers. Suitably normalized leading eigenvalue of these matrices offer a novel characterization of DNA primary sequences, referred to as "DNA profiles". The approach is illustrated on exon 1 of human beta-globin gene.

DNA↗
PubMedDate not supplied

The variable molecular descriptors based on distance related matrices.

Recently variable molecular connectivity index and variable paths have been tested as molecular descriptors in several structure-property regressions. Here we outline the construction of several variable molecular descriptors, derived from the distance matrix and the "reversed" distance matrix. This includes the variable Balaban J index and the "reversed" Balaban index 1/J as well as a novel index 1/JJ derived from J and 1/J. All the variable descriptors mentioned were constructed by augmenting the distance matrix by replacing the diagonal zeroes with the variables x, y, z,.

Journal Article↗
PubMedDate not supplied

Novel shape descriptors for molecular graphs.

We report on novel graph theoretical indices which are sensitive to the shapes of molecular graphs. In contrast to the Kier's kappa shape indices which were based on a comparison of a molecular graph with graphs representing the extreme shapes, the linear graph and the "star" graph, the new shape indices are obtained by considering for all atoms the number of paths and the number of walks within a graph and then making the quotients of the number of paths and the number of walks the same length. The new shape indices show much higher discrimination among isomers when compared to the kappa shape indices. We report the new shape indices for smaller alkanes and several cyclic structures and illustrate their use in structure-property correlations. The new indices offer regressions of high quality for diverse physicochemical properties of octanes. They also have lead to a novel classification of physicochemical properties of alkanes.

Journal Article↗