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Biomedical subjects

H Schulz

Publications and source records attributed to H Schulz.

At least 181 records · Page 10Linked to original sources
PubMed1996

Prenatal exposure to sodium bromide affects the postnatal growth and brain development.

Previous experiments suggest that bromide ions interfere with trophic interactions of neurons in intact adult rats and may modify reactive neuroplasticity during postnatal development. Here we report on bromide effects on normal development. Rat embryos were exposed to sodium bromide (NaBr) by providing an aqueous solution of 250 mg/% NaBr in the drinking water, ad libitum, to their dams. Controls received either tap water or saline (250 mg%NaCl) to drink. Application to dams was restricted to the 5th to 15th days of gestation. Measurements of bromide concentrations in samples of blood and brain homogenates revealed, however, that bromide transfer to embryos was not restricted to the treatment period. Because of delayed excretion dams provided the offspring with bromide via placenta and milk up to 10 days after birth, although at decreasing concentrations. Significant delays in postnatal development were observed in all bromide-treated animals. Permanent deficits were recorded for body weight, brain weight and the protein content of brain tissue. Additionally, there were some changes in brain structure, e.g. the laminar structure of the neocortex was modified. In contrast to developmental deficits, the size of olfactory glomeruli was consistently larger in bromide-treated rats during postnatal and glomeruli attained a mean diameter that was 30 percent larger than in controls at 3 months of age. Results suggest that pre- and perinatal exposure of rats to moderate concentrations of NaBr may interfere with postnatal development including that of brain. Since after complete excretion of bromide developmental deficits persist and show periods of partial compensation and decompensation, induction of these bromide effects is probably indirect. The exact mechanism of bromide action on developmental processes remains to be elucidated.

Age Factors↗
PubMed1995

Peroxisomes contain delta 3,5,delta 2,4-dienoyl-CoA isomerase and thus possess all enzymes required for the beta-oxidation of unsaturated fatty acids by a novel reductase-dependent pathway.

The presence of delta 3,5,delta 2,4-dienoyl-CoA isomerase in peroxisomes was demonstrated by determining the subcellular distribution of this enzyme in rat liver. The peroxisomal and mitochondrial forms of the isomerase exhibit similar chain length specificities and they are homologous as indicated by the recognition of the peroxisomal 66-kDa enzyme by an antiserum raised against the mitochondrial 32-kDa isomerase. This report demonstrates that peroxisomes contain all enzymes required for the beta oxidation of unsaturated fatty acids with odd-numbered double bonds by a novel pathway in which double bonds are reductively removed by the NADPH-dependent 2,4-dienoyl-CoA reductase.

Animals↗
PubMed1995

Short-chain 3-hydroxy-2-methylacyl-CoA dehydrogenase from rat liver: purification and characterization of a novel enzyme of isoleucine metabolism.

Short-chain L-3-hydroxy-2-methylacyl-CoA dehydrogenase (SC-HMAD), a soluble mitochondrial enzyme, was purified 6000-fold from rat liver in 6% yield by a six-step purification procedure. The purified enzyme was homogenous as judged by gel electrophoresis in the presence of sodium dodecyl sulfate. The molecular mass of this protein was estimated to be 28 kDa under denaturing conditions. Under nondenaturing conditions, the enzyme behaved on Sephacryl S-200 like serum albumin with a molecular mass of 66 kDa. Thus, SC-HMAD seems to be a dimer composed of two, most likely identical 28-kDa subunits. Immunoblotting with antibodies to pig heart L-3-hydroxyacyl-CoA dehydrogenase (HAD) (EC 1.1.1.35) revealed that SC-HMAD and HAD are immunologically unrelated proteins. SC-HMAD, but not HAD, catalyzes the NAD(+)-dependent dehydrogenation of L-3-hydroxy-2-methybutyryl-CoA, a metabolite of isoleucine, to 2-methylacetoacetyl-CoA. Relative activities with 3-hydroxy-2-methylacyl-CoA thioesters having acyl chains with 4, 5, 10, and 16 carbon atoms are 88, 100, 16, and 0%, respectively. Unbranched 3-hydroxyacyl-CoA thioesters are also substrates of SC-HMAD, although poorer ones as evidenced by apparent Km values of 5 and 19 microM for L-3-hydroxy-2-methylbutyryl-CoA and L-3-hydroxybutyryl-CoA, respectively. Maximal velocities observed with these two substrates were similar. It is concluded that SC-HMAD catalyzes the second dehydrogenation step during the beta-oxidation of the isoleucine metabolite 2-methylbutyryl-CoA. This enzyme may also be involved in the beta-oxidation of natural and xenobiotic branched chain carboxylic acids.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1995

Mitochondrial beta-oxidation of 2-methyl fatty acids in rat liver.

The mitochondrial beta-oxidation of 2-methyl fatty acids was studied with coupled rat liver mitochondria and purified enzymes. Measurements of mitochondrial respiration supported by 2-methyl fatty acids, straight chain fatty acids, or their coenzyme A (CoA) thioesters revealed that free short-chain and medium-chain 2-methyl fatty acids are oxidized nearly or as efficiently as are their straight chain analogs. Long-chain 2-methyl hexadecanoyl-CoA is also oxidized, although more slowly than its unbranched counterpart. However, medium-chain 2-methyldecanoyl-CoA, in contrast to its unbranched analog, is not oxidized at all. Of all acyl-CoA dehydrogenases only long-chain acyl-CoA dehydrogenase acts on medium-chain and long-chain 2-methylacyl-CoA thioesters. The resultant 2-methyl-2-enoyl-CoA thioesters are substrates of the mitochondrial trifunctional beta-oxidation complex which catalyzes the sequential hydration, dehydrogenation, and thiolytic cleavage of 2-methyl-substituted substrates to yield chain-shortened acyl-CoA thioesters and propionyl-CoA. The matrix enzymes L-3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase, in contrast to enoyl-CoA hydratase, are inactive with medium-chain and long-chain 2-methyl-substituted chain substrates. The specificity of the beta-oxidation enzymes toward 2-methyl-branched substrates forms the basis for assays of long-chain acyl-CoA dehydrogenase and the trifunctional beta-oxidation complex in the presence of their mitochondrial isozymes. It is concluded that rat liver mitochondria can oxidize 2-methyl fatty acids, but does so most effectively with medium-chain and short-chain ones that can enter mitochondria directly in a carnitine-independent manner.

Acyl Coenzyme A↗
PubMed1995

Glutamate 139 of the large alpha-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of delta 3, delta 2-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli.

Multienzyme complexes of fatty acid oxidation from Escherichia coli with either an alpha/Glu139-->Gln or an alpha/Arg134-->Gln mutation in the large alpha-subunit have been overproduced and characterized. The catalytic properties of the five different component enzymes of the alpha/Arg134-->Gln mutant complex showed no significant changes as compared with those of the wild type complex. In contrast, the 3-hydroxyacyl-coenzyme A (CoA) epimerase activity of the alpha/Glu139-->Gln mutant complex was not detected, and this mutant complex has lost almost all of the enoyl-CoA hydratase activity due to a greater than 3000-fold decrease in the kcat of the enoyl-CoA hydratase without a significant change in the Km value. The catalytic properties of 3-ketoacyl-CoA thiolase and L-3-hydroxyacyl-CoA dehydrogenase were virtually unaffected by the mutation. Together, these observations lead to the conclusion that the gamma-carboxylic group of Glu139 functions as a catalytic base in the dehydration of both D- and L-3-hydroxyacyl-CoA. These findings also support a dehydration/hydration mechanism for 3-hydroxyacyl-CoA epimerase but do not agree with an epimerase activity independent of enoyl-CoA hydratase as proposed for the glyoxysomal tetrafunctional protein [Preisig-Müller, R., Gühnemann-Schäfer, K., & Kindl, H. (1994) J. Biol. Chem. 269, 20475-20481]. Since this mutation caused the kcat of delta 3-cis-delta 2-trans-enoyl-CoA isomerase to decrease by only 60%, even though the Km value was significantly increased, it seems that Glu139 of the E. coli multifunctional protein does not function as a catalytic residue in the isomerization reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1995

On the rate-limiting step in the beta-oxidation of polyunsaturated fatty acids in the heart.

This study was conducted to determine if the activity of 2,4-dienoyl-CoA reductase limits the rate of cardiac beta-oxidation of highly unsaturated fatty acids. Although growth hormone treatment of hypophysectomized rats caused a 3-fold increase in the activity of 2,4-dienoyl-CoA reductase, beta-oxidation of docosahexaenoate in cardiomyocytes was not stimulated by this treatment. Since cardiomyocytes oxidized oleic acid more rapidly than docosahexaenoic acid, the utilization of energy did not limit beta-oxidation. Respiration measurements with coupled rat heart mitochondria revealed that the rates of beta-oxidation with palmitoyl-CoA and palmitoylcarnitine as substrates were virtually identical but were 3- to 4-fold higher than the rates obtained with either docosahexaenoyl-CoA or docosahexaenoylcarnitine. Although the activity of carnitine palmitoyltransferase I (CPT I) was 5 times higher with palmitoyl-CoA as substrate than with docosahexaenoyl-CoA, this reaction is only one of several that may limit the beta-oxidation of docosahexaenoic acid. Surprisingly, an incremental inhibition of CPT I resulted in a parallel inhibition of respiration supported by either palmitoyl-CoA or docosahexaenoyl-CoA. This observation agrees with the notion that CPT I may also be a regulatory enzyme in cardiac fatty acid oxidation. It is concluded that the reduction of double bonds by 2,4-dienoyl-CoA reductase does not restrict the cardiac beta-oxidation of highly unsaturated fatty acid, like docosahexaenoic acid.

Animals↗
PubMed1995

Molecular genetics of inherited diseases involving human chromosome 4.

Two molecular genetic strategies have widely been employed to characterize candidate genes for human inherited diseases; identification of disease genes via positional cloning and characterization of altered candidate genes in affected persons. Both approaches allowed to uncover disease genes. A well-known example for positional cloning is the identification of the Huntington's disease (HD) gene on human chromosome 4. In other diseases such as piebaldism, Hurler/Scheie syndrome and a form of autosomal recessive retinitis pigmentosa, the disease gene has first been analyzed and later been localized to human chromosome 4. Steady progress in the human genome project permits to combine affected families pointing to the chromosomal localization of the disease causing defects. Then the genes are investigated that are already mapped to this particular region. Accordingly the achondrodysplasia gene has been identified within six months after its chromosomal localization. In order to evaluate cloned genes as potential candidates for disorders linked to chromosome 4, it is important to assign all genes to chromosomal (sub)regions. Furthermore in excess of 140 closely spaced microsatellites on chromosome 4 as well as many "expressed sequence tags" will help to narrow in on additional disease genes.

Chromosome Mapping↗
PubMed1995

Evidence for intermediate channeling in mitochondrial beta-oxidation.

The accumulation of beta-oxidation intermediates was studied by incubating normal and beta-oxidation enzyme-deficient human fibroblasts with [2H4]linoleate and L-carnitine and analyzing the resultant acylcarnitines by tandem mass spectrometry. Labeled decenoyl-, octanoyl-, hexanoyl-, and butyrylcarnitines were the only intermediates observed with normal cells. Intermediates of longer chain length, corresponding to substrates for the beta-oxidation enzymes associated with the inner mitochondrial membrane, were not observed unless a cell line was deficient in one of these enzymes, such as very-long-chain acyl-CoA dehydrogenase, long-chain 3-hydroxyacyl-CoA dehydrogenase, or electron transfer flavoprotein dehydrogenase. Matrix enzyme deficiencies, such as medium- and short-chain acyl-CoA dehydrogenases, were characterized by elevated concentrations of intermediates corresponding to their respective substrates (octanoyl- and decenoylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency and butyrylcarnitine in short-chain acyl-CoA dehydrogenase deficiency). These observations agree with the notion of intermediate channeling due to the organization of beta-oxidation enzymes in complexes. The only exception is the incomplete channeling from thiolase to acyl-CoA dehydrogenase in the matrix. This situation may be a consequence of only one 3-ketoacyl-CoA thiolase being unable to interact with the several acyl-CoA dehydrogenases in the matrix.

Acyl-CoA Dehydrogenase↗
PubMed1995

Symposium: Cognitive processes and sleep disturbances: The disturbance of cognitive processes in narcolepsy.

Neuropsychological methods have been applied by different authors to investigate cognitive processes such as attention, information processing, memory and psychomotor performance in narcoleptic patients. A review of the results strongly suggests that cognitive processes in narcoleptic patients are not impaired on a functional but only on a temporal level. Providing that short and challenging tasks were used, the performance of narcoleptic patient did not differ significantly from that of healthy subjects. Performance was impaired mainly when a low and monotonous information input had to be processed, a situation which is typical for tests of vigilance. This was supported by this study measuring critical flicker fusion (CFF) at 15-min intervals for 10 hours in 10 narcoleptic patients and matched healthy controls. While peak performance did not differ between groups, narcoleptic patients were unable to perform at a steady level through the day. Tiredness and episodes of sleepiness seem to be the main reason for cognitive impairments in narcolepsy.

Journal Article↗
PubMed1995

Do the B-vitamins exhibit antinociceptive efficacy in men? Results of a placebo-controlled repeated-measures double-blind study.

Additive analgesic effects of long-term application of a combination of the vitamins B1, B6, B12 (thiamine diphosphate 100 mg, pyridoxsine-HCl 200 mg, cyanocobalamin 20 micrograms, p.o.) on a single dose of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac (diclofenac-Na, 50 mg, p.o.) were investigated with a noninflammatory experimental pain model in 38 healthy volunteers. B-vitamins were given with 3 dosages/day for 1 week. Then experimental sessions of 3 h followed to test the analgesic efficacy of the NSAID. In these sessions, phasic pain was induced by intracutaneously applied brief electrical pulses (20 ms). Measured were the pain ratings, the cerebral potentials and the EEG delta power in responses to the stimuli as target variables for the analgesic test. Unspecific effects upon the vigilance system were evaluated by spontaneous EEG, auditory-evoked potentials and reaction times. The investigation was performed as a placebo-controlled, double-blind cross-over study. Blood samples were taken to monitor the plasma concentrations of the active agents. Whereas in the first block of stimuli (40-60 min after diclofenac medication) no analgesic effects of diclofenac could be observed, either given alone or after pretreatment with the B-vitamins, in the second stimulus block (100-120 min after medication) significant effects appeared in all target variables describing analgesia. Pain ratings were decreased by about 5%, late cerebral potentials by about 9% and stimulus-induced delta power of the EEG by about 14%. These effects were significant (p < 0.05, p < 0.01) against those under placebo, but came out to be independent of the B-vitamin pretreatment. No B-vitamin effects of the B-vitamins could be detected, either additive analgesic effects on diclofenac analgesia or on the concomitant variables describing unspecific sedative effects. Clearly the B-vitamin pretreatment for 1 week enlarged the plasma levels for vitamin B6 by 700%, for vitamin B1 by 70% and for vitamin B12 by 50%. All B-vitamin concentrations were independent of each other.

Adult↗
PubMed1995

ECG activity in the sleep of insomniac patients under the influence of lormetazepam and zopiclone.

The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic zopiclone (7.5 mg) on heart rate activity was studied in 16 elderly insomniacs in a placebo-controlled, randomised, 3-fold crossover trial. After digital preprocessing of the ECG, QRS complexes were automatically recognised by a detection technique based on adaptative thresholds. Both R-R periodicity and heart rate variability were analysed as a function of sleep stages and time of night. Under placebo, heart rate decreased significantly from the first to the second half of the night. The relationship between sleep stages and heart rate remained constant under both hypnotics. Although the two substances significantly modified the distribution of sleep stages, no relevant changes in ECG activity were observed when the proportion of the different sleep stages was taken into consideration.

Aged↗
PubMed1995

On the choice of recording duration in pharmaco-EEG studies.

Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances on the central nervous system (CNS) activity. A standard technique is to measure the EEG under vigilance-controlled and resting conditions for a short duration, for example 5 min. The aim of the present study was to investigate the stability of 5-min EEG recordings. While the time course of the EEG was fairly stable during the recording session under the vigilance-controlled condition, systematic trends became apparent under the resting condition. Pharmaco-sensitivity of the EEG and its reliability increased with the recording duration. Five minutes of EEG recording seem to be sufficient and well chosen to evaluate the influence of drugs on the EEG.

Adult↗
PubMed1995

Life-time exposure to dichlorvos affects behaviour of mature rats.

Wistar rats were exposed to dichlorvos [CAS number 62737]. Doses were 1/25; 1/50; and 1/100 LD50, that is 3.88; 1.94; 1.46; and 0.97 mg kg-1 DDVP, respectively, throughout gestation (GD1-birth) and during suckling via oral dosing to the dams, and then via the same doses by gavage for the rest of their lives. The offspring were tested in an open field (OF), a multiple T-maze, and in a 'novelty-induced-grooming' test to assess behavioural competence as adults. Dose-related increases in running time and incorrect choices in the maze were observed during the first 2 weeks of a 3-week study at 9-11 weeks of age. Horizontal activity was increased, vertical activity decreased, and defecation decreased in the OF at 9-12 weeks of age; these changes were again dose-related. Sleep was also affected at 12 weeks of age. AChE activity in the brain and in blood at sacrifice was roughly 40% to 65% of control, again reflecting the doses administered. The significantly changed behavioural profile of DDVP treated rats may serve as a useful biomarker to judge functional damage of CNS properties.

Acetylcholinesterase↗
PubMed1995

[Reduction of the anterior drawer of the knee joint by rehabilitation orthoses. Comparison of the MVP orthosis vs. the Donjoy-Gold point orthosis].

In 20 patients with chronic anterior instability of one knee, two rehabilitation braces (MVP, Donjoy-Gold point) were tested for their ability to limit tibiofemoral translation. A KT-1000 arthrometer was used to quantify the anterior drawer. Both braces significantly reduced passive anterior drawer at 67 N, 89 N and maximal manual shear load and also active anterior drawer. Without a brace the mean anterior drawer was 12.3 mm (67 N), 14.4 mm (89 N), 17.2 mm (maximal manual drawer) and 9.1 mm (active drawer). With the MVP brace the mean anterior drawer was 6.8 mm (67 N), 8.5 mm (89 N), 11.0 mm (maximal manual drawer) and 6.8 mm (active drawer). With the Donjoy brace the mean anterior drawer was 9.2 mm (67 N), 11.0 mm (89 N), 13.1 mm (maximal manual drawer) and 7.4 mm (active drawer). Control values for the non-injured opposite knee were 6.5 mm (67 N), 7.2 mm (89 N), 8.1 mm (maximal manual drawer) and 5.6 mm (active drawer). In direct comparison, the MVP brace provided better stabilization than the Donjoy-Gold point brace did.

Adult↗
PubMed1995

Aerosol bolus dispersion and effective airway diameters in mildly asthmatic children.

The contribution of aerosol techniques, the estimation of aerosol bolus dispersion and effective airway dimensions, to the clinical diagnosis of paediatric asthma was studied. In 47 children, aged 11 +/- 2 yrs, with mild asthma (forced expiratory volume in one second (FEV1) 83 +/- 9% of forced vital capacity (FVC)) effective airway diameters were derived from the recovery of inhaled 1 micron sebacate droplets. Intrapulmonary dispersion of inhaled boluses of 0.4 micron droplets was studied, by characterizing the concentration distributions of droplets in the exhaled air by their standard deviation and skewness. Effective airway diameters increased in asthmatic subjects with increasing body size, and did not differ from those obtained in 16 healthy children of similar age and height. Standard deviation and skewness of particle boluses exhaled from shallow lung depths were higher in the asthmatic children than the healthy children (e.g. standard deviation 91 +/- 17 ml vs 79 +/- 15 ml, skewness 0.38 +/- 0.16 vs 0.23 +/- 0.16, respectively, for boluses in 140 ml lung depth). The sensitivity and specificity of bolus dispersion to detect alterations in lung function was comparable to that of FEV1/FVC, the most sensitive conventional lung function parameter in the present study. There was no correlation between body height or lung function and bolus parameters. We conclude that aerosol measurements do not provide an obvious benefit for the clinical diagnosis of mild paediatric asthma, but bolus dispersion supplies additional information on alterations in convective gas transport in the diseased lung.

Aerosols↗