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Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

At least 415 records · Page 23Linked to original sources

Effect of antemortem and postmortem factors on [3H]glutamate binding in the human brain.

The effect of a number of antemortem and postmortem factors on both N-methyl-D-aspartate (NMDA) sensitive and NMDA insensitive [3H]glutamate binding was investigated in the frontal cortex and putamen of human brains. There was a high correlation between both binding sites (r = 0.86, P less than 0.001) and both binding sites increased during the early postnatal period reaching a maximum between age 1 and 2 years. After age 10 years NMDA sensitive sites disappeared at 9.2% per decade while the NMDA insensitive sites disappeared at 7.4% per decade only. Therefore, the ratio between NMDA sensitive and NMDA insensitive sites changed in favor of the NMDA insensitive site with increasing age. The storage time of brain tissue had a strong reducing effect on both binding sites, again affecting the NMDA sensitive sites more severely. There was no obvious effect of gender, brain weight or postmortem time interval on either binding site. Furthermore, there was no difference between frontal cortex and putamen. Both binding sites were bilateral symmetrically distributed in either frontal cortex and putamen.

Adolescent↗

Factors contributing to fluctuations of the dopaminergic nigro-striatal feedback system in Parkinson's disease.

The experience that the supplementation of depleted dopamine in the nigro-striatal system of parkinsonian patients with L-dopa improves the clinical triad, akinesia, rigidity and tremor, mainly applies to long-term treatment in the early phase of Parkinson's disease. Complications in motor performance, like on-off response, wearing-off phenomena, peak-dose dyskinesia, biphasic dyskinesia, off-period dystonia and others, after more than 3 to 5 years following the onset of treatment indicate fluctuations in the dopaminergic feedback control system. It is suggested that these complications are due to progressive presynaptic degeneration and late changes in postsynaptic receptor amplification. However, as fluctuations are not imperative in all patients, an important additional aspect seems to be the topography of denervation, which involves different portions of the striatum to varying degrees. Location and extent of denervation are criteria which appear to have predictive value for the malignancy of the disease, the therapeutic response of drugs and complications in long-term treatment.

Antiparkinson Agents↗

Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain.

Tyrosine hydroxylase (TH) contents in the caudate nucleus, putamen, and substantia nigra from control and parkinsonism brains were measured for the first time by a sandwich enzyme immunoassay. Both the TH protein content and TH activity (Vmax) were decreased in parallel in the parkinsonian brains as compared with those of the control brains. In contrast, TH "homospecific activity" (activity per enzyme protein) was significantly increased in the parkinsonian brains. The results indicate that the decrease of TH activity in parkinsonian brains is due to the decrease of TH protein content as a result of cell death. The increase in the "homospecific activity" of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.

Brain Chemistry↗

Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain.

Significant differences in the content of iron (III) and total iron were found in post mortem substantia nigra of Parkinson's disease. There was an increase of 176% in the levels of total iron and 225% of iron (III) in the substantia nigra of the parkinsonian patients compared to age matched controls. In the cortex (Brodmann area 21), hippocampus, putamen, and globus pallidus there was no significant difference in the levels of iron (III) and total iron. Thus the changes in total iron, iron (III) and the iron (II)/iron (III) ratio in the parkinsonian substantia nigra are likely to be involved in the pathophysiology and treatment of this disorder.

Aged↗

Endocrine parameters and biogenic amines in relationship to psychopathology after cholinergic drug challenge (RS-86).

The centrally active muscarinic agonist RS-86 elicited a dose-dependent anergic-anhedonic syndrome in a double-blind dose-response study in one healthy volunteer. At 4 and 5 mg, RS-86 induced escape from cortisol suppression by dexamethasone parallel to an increase in prolactin. The time course, as well as the absence of increases in plasma epinephrine and growth hormone, suggests that the changes are not due to nonspecific stress. However, there was a slight increase in plasma norepinephrine, tentatively dependent on the dose of RS-86. In 12-hour urine samples the excretion of 3-methoxy-4-hydroxy-phenylglycol and homovanillic acid tended to decrease in a dose-dependent manner, with a subsequent increase during the following nights. No systematic changes occurred in plasma dopamine, serotonin, and cyclic adenosine monophosphate or in plasma and urinary 3,4-dihydroxyphenylacetic acid or urinary vanillylmandelic acid. The findings are discussed in terms of the cholinergic-adrenergic balance hypothesis of affective disorders and biochemical findings in major depression.

Adult↗

Topographic immunocytochemical mapping of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase in human post mortem brain stem.

Immunocytochemical demonstration of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase was performed in the human brain stem using monoclonal antibodies to monoamine oxidase-A and monoamine oxidase-B and polyclonal antibodies to tyrosine hydroxylase. In most of the brain areas examined, except the serotonergic dorsal nucleus of raphe, the noradrenergic locus coeruleus and the dorsal efferent nucleus of vagus, tyrosine hydroxylase-positive neurons were in greater number than monoamine oxidase-A-stained or monoamine oxidase-B-stained neurons. The dorsal nucleus of raphe showed no tyrosine hydroxylase immunoreactivity, but reacted positively to serotonin- and monoamine oxidase-B antibodies, while monoamine oxidase-A staining was moderate. In none of the investigated brain areas did neurons exclusively react with monoamine oxidase-B antibodies without expressing monoamine oxidase-A in a few neurons, while in some areas neurons expressed both monoamine oxidase-A and tyrosine hydroxylase (locus coeruleus; dorsal efferent nucleus of vagus). The oculomotor nucleus stained only with monoamine oxidase-A antibodies, substantia nigra neurons reacted only with tyrosine hydroxylase antibodies. Glial staining in most of the brain areas examined seemed, with slight differences, to have the same intensity with monoamine oxidase-A and monoamine oxidase-B antibodies used. No glial staining was obtained with tyrosine hydroxylase antibodies.

Aged↗

Tyrosine hydroxylase activity in caudate nucleus from Parkinson's disease: effects of iron and phosphorylating agents.

Tyrosine hydroxylase (TH) activity of human postmortem brain tissues from controls and patients with Parkinson's disease (PD) was examined in the presence of Fe2+ and phosphorylation agents, such as cyclic AMP, exogenous protein kinase, calcium plus calmodulin (Ca2+-CaM), and ATP. TH activity from parkinsonian tissue was increased by 48% with statistical significance in the presence of exogenous protein kinase. Cyclic AMP alone had no effect, whereas Ca2+-CaM increased the activity by only 10%. The presence of acetylcholine resulted in a slight decrease in enzyme activity. Human TH was stimulated 13.17-fold in the presence of 1 mM Fe2+. For iron dependence, no significant differences could be shown for the Km values of TH in striata of PD, while the activity of TH was half of that of controls. Here stimulation with 1 mM Fe2+ raised the activity of TH 11-fold. Stimulation of rat, gerbil, pig, and human caudate nucleus TH with Fe2+ shows remarkable species differences. In particular, the sensitivity of human TH to stimulating processes is noteworthy. H2O2 decreases TH activity only at high concentrations. Species differences are noted for the combined incubation of Fe2+ and H2O2. In the gerbil caudate nucleus, H2O2 does not prevent the stimulating properties of Fe2+, while the pig shows a dose-dependent decline of TH activity. In conclusion, there are no significant changes in the stimulating properties of human caudate nucleus TH activity with Fe2+ in PD, while such differences are noted by using exogenous protein kinase. Furthermore, experimental evidence shows that TH activity declines at high concentrations of H2O2 only. Potentiation of this effect by Fe2+ seems to be species-dependent.

Aged↗

Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia.

Monoamine oxidase-B (MAO-B) activity of platelets of an age- and sex-matched group of controls was compared with several groups of inpatients having non-familial dementia of Alzheimer type (DAT), Parkinson's disease (PD), multi-infarct dementia (MID), mixed types of these 3 diseases and a group of other central nervous system (CNS) organic disorders. All patients were subjected to several psychometric tests, including the Sandoz Clinical Assessment--Geriatric Scale, Hamilton Rating Scale for Depression, Mini-Mental State Examination and the Organic mental Disorder Scale (OMDS). A statistically significant enhancement of MAO-B activity could be observed in DAT patients and in PD patients, whereas the MID group showed a mean activity similar to that of the control group and the group with other organic CNS disorders. In DAT patients the degree of dementia in the OMDS test and the enhancement of MAO activity were positively correlated, but PD did not show such a correlation. It is concluded that the increase of MAO activity in PD and in DAT might be due to a disease-related enhanced affinity to oxygen and to such oxygen-derived radicals as superoxide or hydroxyl radicals. However, a possible drug-induced enhancement of MAO activity in PD cannot be excluded. Furthermore, the MAO-B activity values in platelets of individual patients or controls are not indicative of diagnosis or prognosis of any of these diseases and are of no disease-related specificity.

Adult↗

Changes in cerebral receptors for gamma aminobutyric acid in patients with hepatic encephalopathy.

If the gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system plays an important role in the mediation of hepatic encephalopathy (HE) in man, changes in the status of receptors for GABA in the brain may occur in patients with HE. To test this possibility, brains were obtained at autopsy from 11 patients who had died of causes unrelated to liver disease and from 11 patients who had died with chronic liver disease. Eight of the liver disease group had overt HE at the time of death. The specific binding of GABA to synaptic membranes isolated from frontal cortex was determined. Mean specific binding of GABA for patients with cirrhosis without overt HE was similar to that for control patients. In contrast, corresponding means for patients who had mild HE (stages I-III) and for patients who had severe HE (stage IV) were 45% higher (p less than 0.05) and 43% lower, respectively, than that for control patients. The mean specific binding of GABA was significantly greater for patients with mild HE than in patients with severe HE (p less than 0.025). Scatchard plots of the GABA binding data were curvilinear and consistent with a model of GABA receptors with two independent binding sites. Computer-assisted analysis of the binding data indicated that the altered GABA binding observed in patients with HE is attributable to changes in the affinity rather than the density of both GABA receptors (increased affinities in mild HE, and decreased affinities in hepatic coma). These findings are compatible with the hypothesis that alterations in GABAergic neurotransmission are associated with and contribute to the syndrome of HE in man.

Aged↗

[Schizophrenic psychosis in a patient with Gilles de la Tourette syndrome].

A 36 year-old female patient with schizophrenia and Tourette syndrome is described. Clinical course, present neurological and psychopathological state, results of psychological testing, computed tomography and MR tomography of the skull, EEG and evoked potentials are reported. Results of neurochemical analysis of CSF and plasma are presented. Possible relationships between Tourette syndrome and schizophrenia are discussed with particular reference to neurochemical findings.

Adult↗

[Metabolic changes in ischemic brain infarct].

Serum and cerebrospinal fluid (CSF) from 17 patients less than 3 days after brain infarction (measurement 1) and during recovery 7 +/- 2 days after infarction (measurement 2) were analysed for organic acids (energy metabolites, keto acids and amino acids). Clinical parameters improved by 32% over the period of assessment. Only serum pyruvate levels were elevated at both measurement times. Acute infarction was characterized by significant correspondence of serum and CSF concentrations for pyruvate and alpha-oxo-beta-methyl valeric acid which was lost during the recovery period. Amino acids of the L-system were roughly doubled (phenylalanine 7-fold in the CSF); increased concentrations were recorded for amino acids of the basic transport system, while amino acids of the A-system stayed unchanged (with the exception of alpha-amino butyric acid--20-fold in CSF). Except in the case of taurine, serum and CSF amino acid concentrations remained unchanged between the two measurement times. Mutual dependence of CSF and serum amino acid concentrations, existing initially for glycine, valine, leucine, tyrosine, as well as ornithine, lysine and histidine was lost in the recovery phase. This is interpreted as indication of a normalization of the blood-brain barrier.

Acids↗

Human brain dopamine receptors in children and aging adults.

Since spontaneous oral dyskinesias are more prevalent in the elderly, and since these movements may be controlled by the balance of brain dopamine D1 and D2 dopamine receptors, we measured the densities of these receptors in 247 postmortem brain striata. In childhood, the densities of D1 and D2 dopamine receptors in the brain striatum rise and fall together. After age 20 years, D1 receptors disappear at 3.2% per decade while D2 receptors disappear at about 2.2% per decade. Overall, therefore, the D1/D2 ratio falls with age. Since perioral motion in rats is dominated by a high D1/D2 ratio, the observed decline in the human D1/D2 ratio with age suggests that the perioral control mechanisms for humans and rats may be different.

Aged↗

HPLC analysis of somatostatin related peptides in putamen of Huntington's disease patients.

Size exclusion high performance liquid chromatography of post mortem human putamen samples revealed three somatostatin-immunoreactive peaks. The two major peaks cochromatographed with synthetic somatostatin-14 and somatostatin-28, respectively whereas the presumed somatostatin precursor preceded these peaks. In 11 samples obtained post mortem from patients suffering from Huntington's Disease somatostatin-like immunoreactivity was increased by about 55% in the mean. This increase was mainly due to increases in somatostatin-14 and--to a minor extent--of somatostatin-28, whereas the presumed precursor was not significantly changed.

Adult↗