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Biomedical subjects

C Duyckaerts

Publications and source records attributed to C Duyckaerts.

At least 217 records · Page 12Linked to original sources
PubMed1975

Evidence for cooperative effects in the exchange reaction catalysed by the oxoglutarate translocator of rat-heart mitochondria.

The initial rates of the exchange external oxoglutarate/internal malate through the inner membrane of rat-heart mitochondria, for various concentrations of the two substrates, have been reinvestigated for an extended range of concentrations of the external oxoglutarate. This has been made possible by use of the inhibitor-stop technique that allows 100 times smaller incubation times than the centrifugation-stop technique used previously. Under the experimental conditions the uptake of the external-labelled oxoglutarate into the mitochondrial-matrix space is mediated by the oxoglutarate translocator performing a ono-to-one exchange of the anions oxoglutarate (external) and malate (internal). Two intermediary-plateau regions are observed in the kinetic saturation curve of the translocator by the external oxoglutarate, revealing a complex rate equation which is found to be the product of two one-substrate functions. Analysing these features it is shown that the model, proposed earlier, of a "double carrier" as catalyst in a rapid-equilibrium random bi-bi mechanism, is still applicable but that several external binding sites have to be considered. As already noticed the external and the internal substrates bind to their respective sites independently of each other. Furthermore, some additional requirements imposed by the observed kinetics suggest that the exchange reaction is performed by only one translocator species made of identical interacting subunits. The anion exchange is tentatively viewed as a rotation of a subunit around an axis situated in the plane of the membrane after two independent local configuration changes induced by the binding of the two substrates on this subunit.

Animals↗
PubMedDate not supplied

Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians.

beta A4 deposits occur in the brain of some individuals over 50 years of age. It could be a part of the aging process or indicate a disease found frequently in the elderly. To address this question, beta A4 immunocytochemistry was performed on the brain of 15 nondemented and 5 demented centenarians, some of whom were affected by Alzheimer's disease. We found beta A4 deposits in the parahippocampal and the superior temporal gyri of all the cases, whatever the clinical state. The hippocampus was frequently spared. The lesion density was not correlated with the severity of the mental deterioration. The constant deposition of beta A4 protein in the brain of very old people indicates that this process does not spare a large proportion of this population. This result favors beta A4 accumulation in the brain being an ineluctable age-related process.

Aged↗
PubMedDate not supplied

Beta AP deposition and head trauma.

Head trauma is considered to be a risk factor for Alzheimer's disease, because a high prevalence of beta AP deposits has repeatedly been reported in patients who died within a few days following head injury. To evaluate this statement, we undertook two studies using immunohistochemistry for beta AP and found a surprisingly low prevalence of beta AP diffuse deposits. We first selected 23 patients aged 17-63 years, who died 0-76 days after head trauma. Using beta AP antibody at the usual dilution (1:100), we did not find any deposits. With a high concentration of antibody (dilution 1:2) we found beta AP diffuse deposits in one 46-year-old case. In a second study, 17 patients aged 60-79 years old, who died 1-35 days after head injury, were compared to a control group. We did not find any significant difference in the density of beta AP diffuse deposits between cases and controls using usual dilutions of beta AP antibody. The density of beta AP diffuse deposits was linked only to aging and the presence of senile plaques.

Adolescent↗
PubMedDate not supplied

Microglia, amyloid and dementia in alzheimer disease. A correlative study.

To elucidate the role of microglia in Alzheimer's disease, a clinicopathological study was performed involving 26 cases, the mental status of which had been studied pre mortem by the Blessed test score (BTS). We measured the volume density of CD 68 immunoreactive (IR) microglia, congophilic plaques and Abeta deposits, and the numerical density of neurofibrillary tangles (NFT) in a sample of Area 9 (middle frontal gyrus). Dementia was significantly correlated only with the volume density of Abeta deposits and the numerical density of NFT. The volume densities of microglia and congophilic plaques were strongly correlated. With the intellectual status used as a time scale, IR microglia and amyloid deposits appeared almost simultaneously at an early stage in the pathological cascade and decreased, whereas Abeta and NFT were still accumulating. The intellectual deficit seemed to be more significantly related to the latter two lesions than to the microglia-amyloid complex, that was visible at an earlier stage (around BTS = 15).

Aged↗
PubMedDate not supplied

MRI description of cerebral atrophy in mouse lemur primates.

We assessed cerebral atrophy in mouse lemur primates (Microcebus murinus) by estimating CSF volume in their brains from 4.7 Tesla T2-weighted magnetic resonance images. Thirty animals aged from 1 to 10.3 years were imaged, 14 of them were followed for up to 2 years. Seven of these animals were examined for neuropathology. In 12 out of 17 animals older than 3.5 years, CSF volumes were increased. A subgroup of six animals had severe atrophy of the temporal lobe. Another subgroup of five animals displayed diffuse atrophy in addition to the temporal atrophy. One animal had a dilation of the external part of the temporal horn of the lateral ventricle in addition to the temporal atrophy. The three animals with diffuse atrophy that could be studied for neuropathology had diffuse cerebral amyloid deposits detected by immunocytochemistry. The other animals did not display amyloid deposits. Relations between the different types of atrophy as well as their causes will have to be assessed in future studies.

Age Factors↗
PubMedDate not supplied

Diagnosis and staging of Alzheimer disease.

Rather than determining lesions "threshold" between "normal" cases and patients, we prefer to use clinicopathological correlations, assigning a given intellectual deficit to a given amount of lesions with a chosen level of probability. Because large amounts of A beta diffuse deposits may be found in the absence of dementia, we think advisable not to take them into account for the diagnosis. The diffusion of the neurofibrillary tangles in the paralimbic, limbic and isocortical areas (described by braak and Braak stages or by the number of areas containing tangles) and the density of isocortical senile plaques (A beta focal deposits) as assessed by the CERAD protocol are both correlated with the intellectual status but give complementary information. They should thus be jointly used. We analyzed the variability of the lesions counts, their coefficients of error, and their causes, as a first step toward standardization. We have shown, however, that semiquantitative estimates are presently more reproducible than quantitative measures.

Aged↗
PubMedDate not supplied

Modeling the relation between neurofibrillary tangles and intellectual status.

The relationship between the neurofibrillary tangles and the intellectual deficit observed in senile dementia of the Alzheimer type was studied in 27 patients over the age of 75. The presence and density of tau positive tangles were assessed in six areas including limbic, paralimbic, and isocortical cortices. In the isocortical areas, the presence [1] or absence [0] of neurofibrillary tangles was better correlated with the Blessed test score than the density of the neurofibrillary tangles profiles. Multivariate analysis showed that the number of areas containing at least one neurofibrillary tangle was the best explanatory variable of the intellectual status. The cortical areas were ranked according to the prevalence of their involvement. The presence of tangles in an area of a given rank took place only if the areas of lower ranks were also involved. It is proposed that the presence of tangles in a given area is a more significant information than the value of their density. These data may lead to new diagnostic procedures.

Aged↗
PubMedDate not supplied

Cerebral T2-weighted signal decrease during aging in the mouse lemur primate reflects iron accumulation.

4.7 Tesla T2-weighted magnetic resonance images showed a highly significant signal decrease in the pallidum, substantia nigra, putamen, and a less significant decrease in the thalamus and the caudate of aging mouse lemurs (Microcebus murinus). We evaluated the contribution of iron deposits to the signal decrease comparing Perls' stained histological sections of six mouse lemurs brains aged 1 to 10 years to magnetic resonance images. In young animals, none of the brain structures was stained. A large number of iron deposits were visible in the pallidum and substantia nigra of aged animals and a moderate number in the middle aged ones. In the putamen, few iron deposits were visible in aged and middle-aged animals. The thalamus and the caudate appeared unstained with Perls' technique; iron was too low to be detected. The intensification of the reaction by diaminobenzidine revealed iron deposits in the thalamus of aging animals. This study suggests that in mouse lemurs, iron deposits are responsible for T2-weighted signal decrease in the central gray nuclei.

Aging↗
PubMedDate not supplied

[Fenofibrate induced polymyositis].

In a 65-year old man complaining of myalgias and loss of muscular strength, the creatine phosphokinase level was found to be 35 times higher than normal values. The electromyogram was of the diffuse myogenic type. Muscle biopsy showed necrotic lesions of the muscle fibres associated with perivascular infiltrates of mononuclear cells, leading to the diagnosis of polymyositis. This patient had been treated for 10 years with fenofibrate for hyperlipidaemia; during the last 32 months he had taken this drug in doses of 600 mg per day. Eight days after fenofibrate was discontinued, all clinical and laboratory abnormalities had disappeared. A reintroduction test performed 6 weeks later raised the creatine phosphokinase level up to 43 times the normal value. Withdrawal of fenofibrate therapy resulted in rapid and lasting recovery. This case shows that fenofibrate should be added to the list of drugs that are responsible for iatrogenic polymyositis.

Aged↗