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Biomedical subjects

A Delacourte

Publications and source records attributed to A Delacourte.

177 records · Page 10Linked to original sources
PubMed1977

[Preparation of highly purified microbules and evidence for a novel molecular arrangement at low temperatures].

Microtubules were prepared by in vitro polymerization-depolymerization cycles, 1.0 M NaCl which totally depolymerizes was then added to the preparation. After removal of NaCl new arrangements of tubulin were observed at 4 degrees C: simple and double rings as well as fibrils. At 37 degrees these structures disappeared and tubulin polymerized into microtubules. The highly microtubules contain tubulin, tubulin associated proteins of 300,000 and 330,000 molecular weight, minor proteins of low molecular weight and proteins similar to the Tau factors. This raises a question of the role played by low molecular weight polypeptides. Are they products of proteolysis of rather factors of polymerisation?

Animals↗
PubMed1977

Isolation and characterization of highly purified alpha-1-antitrypsin.

Highly purified human alpha-1-antitrypsin (phenotype MM) was obtained by an original method of preparative electrophoresis. The criteria of homogeneity were assured by one arc in crossed immunoelectrophoresis and one band on polyacrylamide gel. A unique N-terminal amino acid (pyroglutamic acid) and a unique C-terminal residue (lysine) were identified. Determined by gel electrophoresis, its molecular weight was 47,000 daltons.

Amino Acid Sequence↗
PubMedDate not supplied

Dementia in the oldest-old: quantitative analysis of 12 cases from a psychiatric hospital.

To examine the neuropathological characteristics of senile dementia of the Alzheimer type (SDAT) in very old people, we performed a quantitative analysis of the distribution of neurofibrillary tangles and senile plaques in the brains of 12 demented patients aged from 96 of 104 years. The hippocampal formation and the inferior temporal cortex displayed numerous neurofibrillary tangles in most cases, whereas the superior frontal cortex was relatively spared. The only statistically significant difference between demented and control cases was in the density of neurofibrillary tangles in the CA1 field of the hippocampus. High senile plaque densities were observed in the cerebral cortex and were correlated with the duration of SDAT. These results confirm the crucial role of the hippocampus in the neuropathological diagnosis of SDAT in oldest-old patients. Furthermore, they suggest that senile plaque formation may be a pathological hallmark of severe SDAT in this particular age group.

Aged↗
PubMedDate not supplied

Dystrophic neuropeptidergic neurites in senile plaques of Alzheimer's disease precede formation of paired helical filaments.

The relationship between peptidergic neurites and paired helical filaments (PHF)-positive neurites in Alzheimer's disease (AD) senile plaques (SP) was studied using combined fluorescence and bright field optics. Cryostat sections of AD hippocampi were first stained by thioflavine-S and immunolabeled with antisera raised against different neuropeptides: somatostatin 28(1-12) (som 28(1-12)), somatostatin 14 (som 14), neuropeptide Y (NPY), cholecystokinin (CCK) and substance P (sP). Secondly, using the elution-restaining procedure, sections were immunolabeled with anti-tau/PHF. In immature SP, clusters of abnormal, swollen neurites were found. The dystrophic, strongly peptidic-positive neurites contained less PHF than the poorly positive ones. Cell bodies, exhibiting a peptidic content, could be found within SP without any alteration. These results suggest the following sequence of events: an extracellular poisoning mechanism, perhaps the amyloid substance, first changes the structure of presynaptic endings and causes the formation of ballooning dystrophic neurites filled with their normal peptidic content. Subsequently, intracellular degradation occurs with formation of the PHF. Then the other structures such as dendrites and perikarya are damaged by the same mechanism. Therefore this phenomenon seems to precede any formation of PHF in SP.

Alzheimer Disease↗
PubMedDate not supplied

[Immunohistochemical study of the basic lesions of Alzheimer's disease].

Alzheimer's disease is characterized by the presence of two argentophilic histopathologic brain lesions: neurofibrillary tangles (NFT) and senile (neuritic) plaques (SP). NFT consist of large perikaryal masses of abnormal cytoplasmic fibers, most of which have the ultrastructural appearance of pairs of intermediate-sized (10 nm) filaments wound into a double helix and named Paired Helical Filaments (PHF). PHF also occur within the degenerating neurites of SP. The insolubility of PHF in strong detergents is turned to account for their isolation. We have isolated these structures from an Alzheimer brain and raised antibodies against PHF. The anti-PHF antibodies detected specifically NFT and SP on nervous tissue sections of Alzheimer brains, and also NFT in the hippocampus of normal aged brains. The stainings of NFT and SP by the anti-PHF or the classical Bodian silver staining technique were compared. The immunohistochemical method is more precise, more reproducible, more specific and will be of great interest for the quantification of these structures, specially when they are in minor quantities particularly in the atypical disease. Furthermore, the anti-PHF antibodies did not visualize neurofilament containing structures, and did not react with neurofilament protein subunits on immunoblots. These results are compared to those reported in the literature.

Adult↗
PubMedDate not supplied

[Physiopathological bases of Alzheimer disease].

Alzheimer's disease is characterized by the presence of two types of brain lesions: senile plaques and neurofibrillary degeneration. A peptide named beta A4 is the major component of the amyloid substance that constitutes senile plaques. beta A4 is part of a much larger membrane-associated protein known as the amyloid protein precursor (APP) whose gene is on chromosome 21. Mutations on APP gene have been linked to several early-onset AD families, demonstrating the pathogenicity of APP. The amyloid substance, likely neurotoxic, provokes a cascade of biochemical dysfunctions that leads to neurofibrillary degeneration (NFD). NFD is characterized by an intraneuronal filamentous accumulation of abnormally phosphorylated Tau proteins and is followed by cell death. NFD probably first affects the hippocampal region and spreads later to the entire isocortex, progressively provoking an intellectual impairment. Together, these observations show that experimentally-induced lesions in animal or cell models, already at our disposal, will open diagnostic and therapeutical perspectives.

Adolescent↗
PubMedDate not supplied

[Diagnosis of Alzheimer's disease].

Alzheimer's disease is a neurodegenerative disorder leading to cognitive impairment (amnesia, aphasia, apraxia and agnosia). The prevalence of this age related disabling illness is increasing. During the course of the disease, the clinical diagnosis will be that of "possible Alzheimer's disease", then "probable Alzheimer's disease". But the diagnosis of "definite Alzheimer's disease" requires a post-mortem brain examination and the demonstration of numerous senile plaques and neurofibrillary tangles in hippocampal and association cortical areas. The neuropathological examination confirms probable Alzheimer's disease clinical diagnosis in 85% of the cases examined in medical schools. However, with much more than 15% errors, the early diagnosis of Alzheimer's disease must be improved since it is a key factor for the therapeutic approach, and more especially for the efficiency of drug trials. At the present time, there are new leads for a biological diagnosis in the blood or the CSF. However, the natural (and molecular) history of Alzheimer's disease points out that all biochemical dysfunctions remain in the CNS, and more particularly in association brain areas. This is demonstrated using reliable biochemical markers such as A beta and pathological Tau proteins, which are the basic components of amyloid deposits and neurofibrillary tangles, respectively. Also, a genetic diagnosis can be performed in half of familial autosomic dominant Alzheimer's disease, which represents less than 1% of all Alzheimer's disease cases. Together, this shows that there is a lack of reliable Alzheimer's disease markers. The search for new specific markers (clinical, epidemiological, genetic, biochemical, biological) must go on.

Alzheimer Disease↗