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Biomedical subjects

G Somjen

Publications and source records attributed to G Somjen.

At least 19 recordsLinked to original sources

Vesicular cholesterol in bile. Relationship to protein concentration and nucleation time.

A study was done to determine whether the nucleation time was related to the amount of cholesterol carried in vesicles. Bile was obtained from cholesterol gallstone patients and controls. Gel-exclusion chromatography was used to separate vesicles and micelles in the native bile using an eluting buffer containing 10 mM sodium cholate. The percent of total cholesterol carried in vesicles in gallbladder bile of stone patients was significantly greater than that in control patients. Total cholesterol concentration in gallbladder bile of stone patients was significantly greater than in controls. This difference was due to the fact that vesicular cholesterol concentration was significantly greater in the gallbladder bile of stone patients compared to controls. Micellar cholesterol concentrations were similar in the two groups. Nucleation time was related significantly to vesicular cholesterol concentration in correlation analysis and, as previously shown, so was total protein concentration. This study supports the importance of vesicular cholesterol in solid crystal formation and demonstrates for the first time that the rate of cholesterol monohydrate crystal formation is directly related to the amount of cholesterol transported in vesicles.

Adult

Effect of vaso-active intestinal polypeptide on systemic and splanchnic haemodynamics: role in vasodilation following mesenteric ischaemia.

Vaso-active intestinal polypeptide (VIP) and the related peptide, peptide histidine isoleucine, were infused intravenously in anaesthetized sheep. The VIP doses were designed to reproduce plasma concentrations seen after mesenteric ischaemia. The vasodilator action of VIP varied between different segments of the circulation and these differences in sensitivity were observed for both the degree and duration of the vaso-active action. A sustained vasodilation was detected in the coeliac artery and portal vein vascular beds during a 30-min VIP infusion. VIP is likely to be a contributory factor involved in the development of circulatory collapse during reperfusion after experimental mesenteric ischaemia.

Animals

Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones.

Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days +/- 0.7) as from patients with stones (2.4 days +/- 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.

Bile

Direct and relayed projection of periodontal receptor afferents to the cerebellum in the ferret.

Field potentials in the cerebellar cortex of the ferret have been studied in response to stimulation of alveolar, muscular and cutaneous branches of the trigeminal nerve. Responses from the alveolar nerves are unusual in their very short latency. Evidence based on latency analysis, frequency following and comparison with other well-known inputs supports the view that the earliest field potentials are due to direct, unrelayed afferents, which terminate as mossy fibres. There is, in addition, a monosynaptically relayed afferent path via mossy fibres. The alveolar nerve afferents concerned with the direct projection are shown to come from periodontal mechanoreceptors and not from cutaneous receptors. No such connections are found from jaw-muscle spindle afferents. The direct and relayed periodontal pathways are both ipsilateral and crossed. They terminate in the cerebellar cortex in the parvermal region of lobules IV, V and VI. The functional significance of the direct periodontal afferent projection is considered particularly in the light of parallels with the vestibular system, which also has direct and relayed cerebellar projections.

Afferent Pathways

Focal synaptic potentials due to discrete mossy-fibre arrival volleys in the cerebellar cortex.

The previously described direct and relayed projections of periodontal afferents to the cerebellar cortex have been examined in detail by extracellular field-potential analysis. Advantage is taken of the very small temporal dispersion of the afferent volleys to permit identification of the presynaptic spike potential of mossy fibres, the subsequent synaptic potential and the firing of granule cells. Changes in form of the presynaptic potential with depth are compared with published descriptions of presynaptic potentials elsewhere. The negative synaptic potential in the granular layer is shown to have a positive aspect in the molecular layer. Granule-cell firing can, under some conditions, yield a population spike interrupting the synaptic potential wave. Records are presented showing all-or-none complex waves, which appear to be single glomerular potentials, not previously described in the mammalian cerebellum. Their distinction from cellular spike potentials is emphasized.

Afferent Pathways

Oxidative metabolism, extracellular potassium and sustained potential shifts in cat spinal cord in situ.

Changes in the ratio of reduced/oxidized cytochrome a,a3 were measured by reflection spectrophotometry in decerebrate cat spinal cord during microelectrode monitoring of extracellular K+ and extracellular potential. In 'resting' cord, cytochrome a,a3 was approximately 60% reduced, compared to 30% in cerebral cortex and 1% in isolated mitochondria. Stimulation of a dorsal root or afferent nerve caused linearly correlated responses, consisting of oxidation of cytochrome a,a3, elevation of K+0 and a negative shift of potential. In spinal cord, unlike cerebral cortex, the local volume of blood increased upon stimulation. The rate of recovery of the oxidation response of cytochrome a,a3 was consistently faster in cord than in cortex. Pentobarbital (i.v.) in anesthetic dosage reduced the amplitude and slowed the rate of recovery of all 4 parameters, indicating that the optical signals originate from gray matter. It is speculated that the spinal cord, even more than cortex, may depend for its viability on the maintenance of PO2 above a certain level, and that much of the metabolic activity following stimulation is associated with the restoration of ionic gradients.

Afferent Pathways

LSD's effect on neuron populations in visual cortex gauged by transient responses of extracellular potassium evoked by optical stimuli.

The effects of systemic LSD (10--25 micrograms/kg) on visually evoked [K+]o responses from the striate cortex have been investigated in cats. Elevation of [K+]o was dependent on the orientation, and direction of stimulus movement and showed ocular dominance. LSD most commonly produced a depression of [K+]o transients and a deterioration in their directional selectivity. These observations suggest that the effect of LSD is to produce a net depression in visually evoked neuronal firing.

Animals

The projection of jaw elevator muscle spindle afferents to fifth nerve motoneurones in the cat.

1. By spike-triggered averaging of intracellular synaptic noise it has been shown in pentobarbitone anaesthetized cats that jaw elevator muscle spindle afferents with their cell bodies in the mid-brain have a relatively weak monosynaptic projection to masseter and temporalis motoneurones. 2. Extending the spike-triggered averaging method to recording extracellular excitatory field potentials it has been shown that virtually all the spindles do project monosynaptically to the motoneurone pool. It is concluded that the general weakness of the projection is due to its restriction to a small proportion of the motoneurones, possibly those concerned most with tonic postural functions. 3. The shape of individual intracellular e.p.s.p.s together with the spatial distribution of extracellular excitatory potential fields provide some evidence for a dentrically weighted distribution of the synapses. 4. Evidence is presented that both primary- and secondary-type spindle afferents project monosynaptically, the secondary effects being some 71% of the strength of the primary ones.

Action Potentials

Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord.

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.

Animals

The transmission of reflexes in the spinal cord of cats during direct irradiation with microwaves.

The spinal of cats was directly exposed to 2450 CW microwave radiation in order to study the effect on reflex response and synaptic function. A small but statistically significant increase in the reflex response was detected in the first series of experiment, which indicates enhancement of the synaptic transmission. However, this effect was not observed in a second series of experiments in which the incident power density was increased from 10 mW/cm(2) to 20 mW/cm(2) and a more rigorous experimental design was employed. The slight changes that were observed in the second series could be attributed to small temperature variations during the experiment.

Animals

Improved voiding in response to electrical stimulation of the spinal cord of paraplegic dogs.

Bipolar electrodes were inserted into the conus medullaris and attached to the proximal urethra of paraplegic dogs. Repeated stimulus trains were delivered to the spinal cord electrodes and the urethral electrodes in an attempt to improve voiding induced by cord stimulation. The results indicate that the increased outflow resistance which often accompanies electromicturition can be significantly overcome both by repeated spinal cord stimulation and by prestimulation of the proximal urethra.

Animals

Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats.

We measured simultaneously the oxidative metabolic activity, monitored as the tissue fluorescence attribute to intramitochondrial NADH, the extracellular potassium level with ion-selective microelectrodes, and the focal extracellular electrical potential, of one site in intact cerebral cortex of cats. When the cerebral was stimulated by trains of repeated electric pulses applied either directly to its surface or to an afferent pathway, the corrected cortical fluorescence (F-R) declined indicating oxidation of NADH, the activity of extracellular potassium [K+]o increased, and the extracellular potential (Vec) shifted in the negative direction. When mild to moderate stimuli not exceeding 10-15 sec in duration were used, a 3-fold correlation was found between these three variables. The regression of F-R over either Vec, or over log [K+]o had a positive ordinal intercept. The results are in agreement with earlier suggestions 4,24,25,43,45,46 that (a) much but not all the oxidative metabolic response of cortex to electrical stimulation is expended in restoring disturbed ion balance; and (b) that sustained shifts of potential (SP) in response to repetitive electrical stimulation are generated by glia cells depolarized by excess potassium. The magnitude of SP shifts associated with a given elevation of [k+]o are smaller in cerebral cortex than in spinal cord48,49. The correlation of F-R with [K+]o breaks down when pathologic processes of either seizure activity or spreading depression set in. During paroxysmal activity [K+]o tends to remain confined below 10-12 mM, a level observed in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing tissue. This observation is hard to reconcile with the suggestion that excess potassium is a factor in the generation of seizures, at least of the type observed in this study. When [K+]o levels exceeded 10-12 mM, spreading depression invariably followed at least under the unanesthetized condition in these experiments. During spreading depression [K+]o levels rose to exceed 30 mM, sometimes 80 mM. NADH was oxidized during spreading depression to a level comparable to that seen in seizures. The observations are compatible with the suggestion13 that spreading depression occurs whenever the release of potassium into extracellular fluid is overloading its clearance therefrom.

Animals