Deep inelastic collision followed by disassembly in the reaction 136Xe+209Bi at Elab/A=28.2 MeV.
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Biomedical subjects
Publications and source records attributed to H Schulz.
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Noninvasive cardiac output (CO) measured by arterial pulse analysis was compared with that measured by inert gas rebreathing in six healthy male volunteers. Pulse contour analysis was applied to the pressure wave output of a Finapres, which noninvasively measures continuous arterial pressure in a finger. Data were collected before, during, and after a 10-day 6 degrees head-down tilt experiment. Intravenous saline loading and lower body negative pressure stimuli varied CO over 2.8-9.6 l/min, as measured by the rebreathing technique. Because pulse contour provides only relative changes in CO, to obtain absolute values it must be calibrated against another measurement. Pulse contour data were calibrated every measurement day against the mean of two to four control rebreathing CO measurements before the lower body negative pressure or intravenous saline loading stimuli. Using one averaged calibration factor per subject for a total of 27 days, we compared the results of both methods. The linear regression between pulse contour (Pc CO) and rebreathing CO (Rebr CO) was Pc CO = 0.15 + 0.98(Rebr CO) (r = 0.96). The standard deviation of the difference of the two methods was 0.5 l/min (n = 205), excluding data used for calibration. By monitoring pulse contour CO before and during rebreathing, the rebreathing maneuver itself was shown to produce a substantial increase in CO that was mainly related to an increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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We investigated the characteristics of periodic leg movements (PLM) during nocturnal sleep and wakefulness in 13 drug-free patients presenting with the restless legs syndrome (RLS, n = 9) or with isolated PLM (n = 4). Eight-hour polygraphic sleep recordings included the electromyogram (EMG) of both tibialis anterior muscles. Scoring of leg movements was done according to established criteria for periodic movements in sleep, but movements occurring during episodes of wakefulness were scored as well. Twelve out of 13 patients had PLM during wakefulness, including three subjects not affected by RLS. The frequency of periodic movements in sleep (PMS) per hour of total sleep time was significantly lower than the frequency of PLM (including movements during wakefulness) per hour of polygraphic recording. Movement indices based on PMS alone underestimated the relative frequency of PLM particularly in patients with high amounts of wakefulness (> 20%). All features of PLM clearly differed between sleep stages. Relative frequency of movements, their duration and their arousing effect decreased along the nonrapid eye movement (NREM) sleep stages, whereas the intermovement interval increased. During rapid eye movement (REM) sleep the duration of movements was shortest and the intermovement interval was longest. The results presented suggest that the processes underlying PLM are most active at the transition from wakefulness to sleep and considerably attenuated during deep NREM sleep and even more during REM sleep. We suggest including movements during wakefulness in routine PLM scoring to get a more complete picture of the disturbance.
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This article sums up the scientific results of the past 10 years on narcolepsy reflecting its impact on socio-medical impairment of narcoleptic patients. Extensive epidemiological studies showed that major restrictions for narcolepsy patients are caused by daytime sleepiness and sleep attacks with consecutive cognitive and memory deficits high accident rates, personality, mood and sexual disorders. We suggest the minimum degree of impairment as a rule should be at least 50%, in case of drug-resistant cataplexy or permanent sleep attacks around 80%.
The kinetics of bovine liver enoyl-CoA hydratase (EC 4.2.1.17) or crotonase with 2-trans-hexadecenoyl-CoA as a substrate were studied because different rates were obtained with two assay methods based on measurements of substrate utilization and product formation, respectively. L-3-Hydroxyhexadecanoyl-CoA, the product of the crotonase-catalyzed hydration of 2-trans-hexadecenoyl-CoA, was found to be a strong competitive inhibitor of the enzyme with a Ki of 0.35 microM. In contrast the short-chain product, L-3-hydroxybutyryl-CoA, is a weak competitive inhibitor with a Ki of 37 microM. L-3-Hydroxyhexadecanoyl-CoA is a much stronger inhibitor of crotonase than are other short-chain and long-chain intermediates of beta-oxidation and crotonase is more severely inhibited by this compound than are all beta-oxidation enzymes tested so far. Determination of true kinetic parameters for the crotonase-catalyzed hydration of long-chain substrates requires the removal of product in a coupled assay. When this was done, the Km for 2-trans-hexadecenoyl-CoA with bovine liver crotonase was found to be only 9 microM. It is suggested that under conditions of restricted beta-oxidation, when 3-hydroxyacyl-CoAs accumulate in mitochondria, the inhibition of crotonase by long-chain 3-hydroxyacyl-CoAs may limit the further degradation of medium-chain and short-chain intermediates of beta-oxidation.
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The mitochondrial metabolism of 5-enoyl-CoAs, which are formed during the beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms, was studied with mitochondrial extracts and purified enzymes of beta-oxidation. Metabolites were identified spectrophotometrically and by high performance liquid chromatography. 5-cis-Octenoyl-CoA, a putative metabolite of linolenic acid, was efficiently dehydrogenated by medium-chain acyl-CoA dehydrogenase (EC 1.3.99.3) to 2-trans-5-cis-octadienoyl-CoA, which was isomerized to 3,5-octadienoyl-CoA either by mitochondrial delta 3,delta 2-enoyl-CoA isomerase (EC 5.3.3.8) or by peroxisomal trifunctional enzyme. Further isomerization of 3,5-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA in the presence of soluble extracts of either rat liver or rat heart mitochondria was observed and attributed to a delta 3,5,delta 2,4-dienoyl-CoA isomerase. Qualitatively similar results were obtained with 2-trans-5-trans-octadienoyl-CoA formed by dehydrogenation of 5-trans-octenoyl-CoA. 2-trans-4-trans-Octadienoyl-CoA was a substrate for NADPH-dependent 2,4-dienoyl-CoA reductase (EC 1.3.1.34). A soluble extract of rat liver mitochondria catalyzed the isomerization of 2-trans-5-cis-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA, which upon addition of NADPH, NAD+, and CoA was chain-shortened to hexanoyl-CoA, butyryl-CoA, and acetyl-CoA. Thus we conclude that odd-numbered double bonds, like even-numbered double bonds, can be reductively removed during the beta-oxidation of polyunsaturated fatty acids.
A study of the activation of valproic acid (2-n-propylpentanoic acid) by a soluble extract of rat liver mitochondria in the presence of ATP, CoASH, and MgCl2 revealed that, in addition to valproyl-CoA, an unknown UV-absorbing compound is formed which is the sole product when CoASH is omitted from the incubation mixture. The unknown compound, which was purified by high performance liquid chromatography, was identified as valproyl adenylate (valproyl-AMP) by mass spectrometry and by its enzymatic conversion to valproyl-CoA in the presence of CoASH. Valproyl-AMP exists, at least partially, in a free, not-enzyme-bound form. Its rate of formation is linear with time and increases 5-fold when the pH is decreased from 8 to 6.8. Valproyl-AMP was also identified when the metabolism of valproate was investigated with rat liver mitochondria and rat hepatocytes. Since the synthesis of valproyl-AMP is inhibited by octanoate, medium-chain acyl-CoA synthetase (EC. 6.2.1.2) may be responsible for its formation. This study establishes that during the activation of valproic acid to valproyl-CoA free valproyl-AMP is formed which is a novel cellular metabolite of valproic acid.
A radioactive method for assaying 2,4-dienoyl-CoA reductase, also referred to as 4-enoyl-CoA reductase (EC 1.3.1.34), is described. The assay measures the incorporation of tritium from [4B-3H]NADPH into 2-trans,4-cis-decadienoyl-CoA or 2-trans,4-trans-decadienoyl-CoA which, after cleavage of the thioester bond with hydroxylamine, can be separated from the radioactive coenzyme by extraction with toluene. This assay is at least 30 times more sensitive than the spectrophotometric assay, even though rates determined by the radioactive method are 10 times lower than rates obtained spectrophotometrically due to a primary kinetic isotope effect. The linearity of this assay with respect to time and protein concentration is sufficient for determining 2,4-dienoyl-CoA reductase activities in extracts from small samples of human fibroblasts, which were found to contain reductase activities between 1.8 and 5.8 mU/mg of protein.
In order to determine if renin release would be affected by a dysfunction of the circadian and ultradian organization of sleep, 24-hour profiles of plasma renin activity (PRA) concomitant with sleep stages were established in 10 normal subjects and nine narcoleptic patients, with 10-minute blood sampling intervals. Mean PRA levels were similar in control subjects and narcoleptic patients. Individual 24-hour profiles revealed that the previously described association between renin oscillations and sleep stage alternations was preserved. Increased PRA release was observed during the transition from rapid eye movement (REM) sleep or waking periods to nonrapid eye movement (NREM) sleep, and REM sleep occurred as PRA levels were decreasing. Thus, PRA curves exactly reflected the irregularities and disturbances in the sleep structure of the narcoleptic patients. The 24-hour PRA profiles of the patients did not show the general upward trend during nighttime sleep, which is probably induced in the control subjects by the repetitive recurrence of longer episodes of undisturbed NREM sleep. Because of marked sleep fragmentation in the patients, the duration of NREM sleep was often insufficient to allow for the occurrence of a significant PRA increase. Because sleep onset REM (SOREM) episodes, characteristic of narcolepsy, are not preceded by NREM sleep and its associated increase in PRA, no relative PRA decline occurred during this type of REM sleep. In conclusion, the 24-hour PRA profiles of the narcoleptic patients reflected exactly their sleep stage distribution, confirming previous findings that PRA oscillations appear to be inseparable from the NREM-REM sleep cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
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The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.
The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearson's correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.
There is evidence for two types of sleep spindle activity, one with a frequency of about 12 cycles/s (cps) and the other of about 14 cps. Visual examination indicates that both spindle types occur independently, whereby the 12-cps spindles are more pronounced in the frontal and the 14-cps spindles in the parietal region. The purpose of this paper is to provide more information about the exact topography of these patterns. First the occurrence of distinct signals in anterior and posterior brain regions was verified using pattern recognition techniques based on matched filtering. Thus the existence of two distinct sources of activity located in the frontal and parietal region of the brain, respectively, was demonstrated using EEG frequency mapping. Evaluation of sleep recordings showed high stability both in the frequency and location of the presumed spindle generators across sleep. Pharmacological effects of lormetazepam and zopiclone on both spindle types were investigated. Both substances enhanced the sleep spindle activity recorded from the frontal and parietal electrodes, but this increase was more pronounced in the parietal brain region.