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Biomedical subjects

J Flament-Durand

Publications and source records attributed to J Flament-Durand.

At least 19 recordsLinked to original sources

Distribution and expression of the alpha-tubulin mRNA in the hippocampus and the temporal cortex in Alzheimer's disease.

The distribution of the messenger RNA for alpha-tubulin has been investigated by in situ hybridization in the human hippocampus and temporal cortex in normal subjects and in Alzheimer's disease. The alpha-tubulin mRNA was strongly expressed in neurons in the gyrus dentatus, in the Ammon's horn and in cortical layers of the temporal cortex. The same distribution was observed in Alzheimer's disease. An important reduction of the hybridization signal was apparent, however, in areas rich in neurofibrillary lesions, e.g. as in layer II of entorhinal cortex. Neurons containing neurofibrillary tangles exhibited a weaker hybridization signal than adjacent neurons devoid of neurofibrillary tangles. The immunoreactivity for alpha-tubulin was drastically reduced in tangles-bearing neurons. These results indicate that tubulin transcription is reduced in tangles-bearing neurons, a reduction which might play a role in the reported decrease in the number of microtubules in neurons containing neurofibrillary tangles.

Aged↗

Proximal deletion of chromosome 21 confirmed by in situ hybridization and molecular studies.

Foetal blood sampling was performed at 35 weeks of gestation due to abnormal foetal ultrasound findings. There was apparent monosomy 21 (45,XX,-21) in all mitoses analyzed. The infant died at 37 weeks during delivery. Examination disclosed facial anomalies, clubfeet, hypoplasia of the left urogenital tract, agenesis of corpus callosum, ventricular dilatation, and heterotopias. Reevaluation of the karyotype showed an unbalanced translocation t(1;21) (q44;q22.11) which resulted from a maternal balanced translocation. These findings were confirmed by fluorescence in situ hybridization and molecular studies with chromosome 21 specific markers. The latter showed a proximal deletion of the maternally derived chromosome 21 including all loci from centromere down to the D21S210 locus. This case illustrates the need for complementary cytogenetic and molecular investigations in cases of apparent monosomy 21.

Abnormalities, Multiple↗

Prognostic scoring in adult astrocytic tumors using patient age, histopathological grade, and DNA histogram type.

High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.

Adolescent↗

Pineal cyst: normal or pathological?

Review of 500 consecutive MRI studies was undertaken to assess the frequency and the appearances of cystic pineal glands. Cysts were encountered in 2.4% of cases. Follow-up examination demonstrated no change in these cysts and they were considered to be a normal variant. Size, MRI appearances and signs associated with this condition are reported in order to establish criteria of normality.

Adolescent↗

Cylindrical spinal meningioma. A case report.

A case of cylindrical spinal meningioma is reported. This most unusual morphology suggested a preoperative diagnosis of either lymphoma, metastatic epidural tumor, or meningioma. At operation, the tumor was found to be hard and extremely adherent to the cord, so its anterior part had to be left in place. Transient paraplegia was observed postoperatively, but the patient recovered normal stance and gait within 6 months. Three years after the operation, magnetic resonance imaging demonstrated a very slow progression of the remaining tumor with an estimated increase of 5%. The differential diagnosis of this lesion by magnetic resonance, its clinical postoperative evolution, and the surgical strategy are discussed.

Aged↗

Characterization of nuclear DNA content, proliferation index, and nuclear size in a series of 181 meningiomas, including benign primary, recurrent, and malignant tumors.

The characterization of nuclear area, the proliferation index, and nuclear DNA content was carried out by means of digital cell image analysis, which makes it possible to compute morphometric and densitometric features on Feulgen-stained nuclei from archival, that is, formalin-fixed, paraffin-embedded materials. The 181 meningiomas studied included 173 classic (41 meningotheliomatous, 27 fibroblastic, 82 transitional, nine psammomatous, eight angiomatous and six hemangioblastic tumors) and eight malignant meningiomas (three hemangiopericytomas and five tumors that we labeled HFM, that is, tumors exhibiting evidence of histological features of malignancy). The results reveal a strong relationship between incomplete surgical resection and recurrence on the one hand and between the probability of recurrence and histopathological type on the other. Whereas neither nuclear area nor nuclear DNA content assessments were helpful in distinguishing the six classic and the two malignant meningioma subgroups, a statistically significant increase in proliferative activity was observed in the malignant meningiomas as compared with classic ones, excepting hemangioblastomas that proliferate at the same rate as the malignant meningiomas. Furthermore, the multiple meningiomas definitely proliferated more actively than the single ones, but a similar proliferative activity was observed in the nonrecurrent and recurrent meningiomas. Proliferation analyses might be therefore helpful for determining aggressive meningiomas and for planning adjuvant therapy in these cases.

Adult↗

Positron emission tomography and histopathology in Creutzfeldt-Jakob disease.

We studied a 62-year-old man with Creutzfeldt-Jakob disease (CJD), using positron emission tomography (PET) and (18F)-2-fluoro-2-deoxy-D-glucose (FDG). Glucose metabolism was heterogeneously decreased throughout the brain. At autopsy, regional distributions of spongiosis, astrogliosis, and neuronal loss correlated with premortem regional metabolic deficits. These results suggest that PET with FDG may provide metabolic regional markers for CJD neuropathology.

Brain↗

Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients.

BACKGROUND: The authors studied the benefit of performing histopathologic grading and DNA ploidy characterization with respect to patient survival in a series of 206 astrocytomas (AST) for which they obtained 134 complete clinical follow-ups. METHODS: The material analyzed came from archival material, i.e., formalin-fixed paraffin-embedded tissues. DNA ploidy was assessed by means of a cell image processor computing the integrated optical density (IOD) on Feulgen-stained nuclei. RESULTS: Results showed that histopathologic diagnosis in three grades, i.e., AST, anaplastic astrocytoma (ANA), and glioblastoma multiforme (GBM), had a significant prognostic value. Patients with AST showed a mean survival time (between histopathologic diagnosis and death) of more than 36 +/- 6 months (AST versus ANA or GBM) (P less than 0.001). Patients with ANA and GBM showed a mean survival time of 15 +/- 2 and 10 +/- 1 months, respectively, (ANA versus GBM) (P less than 0.05). Patient age strongly correlated with survival. Patients younger than 40 years of age had a mean survival time of 20 +/- 4 months. Patients between 41 and 60 years of age had a mean survival time of 12 +/- 2 months, and patients older than 60 years of age had a mean survival time of 11 +/- 1 months. CONCLUSIONS: Considering DNA ploidy characterization, the authors noticed that aneuploid ANA (DNA index [DI] more than 1.30) were associated with a significantly higher mean patient survival time compared with that associated with euploid ANA. In contrast, the authors did not find this in either of the groups with AST and GBM. Recognizing six DNA histogram types (diploid, triploid, tetraploid, hyperdiploid, hypertriploid, and polymorphic), the authors observed that hypertriploid tumors were associated with greater patient survival compared with what happened in the cases of the five other DNA histogram types. This was true with respect to the three AST histopathologic types. Thus, DNA ploidy determination seemed helpful in characterizing aggressiveness in adult AST.

Adolescent↗

What's new in the pathology of neuronal cytoskeleton: the significance of neurofibrillary tangles.

Neurofibrillary tangles are a neuronal change observed in various conditions, linked with dementia when affecting the cerebral cortex as in Alzheimer's disease. They may be found locally close to fibrous or vascular tumors, or affect extensive regions of the neocortex while the cerebellum and the medulla are not affected. Recent immunological and biochemical studies demonstrate that the MT-associated protein tau is the main component of the tangles, in an abnormally phosphorylated state. A consequence of the formation of tangles is a decreased assembly of MT in axons and dendrites, with disturbances of neuroplasmic flow. The relations between tangles and amyloid, as seen in Alzheimer's and Down's diseases are topographical, tangles accumulating in particular in neurites close to the amyloid in the senile plaques (but also at distance in cell bodies and neurites). Genetically and biochemically A4 or beta-amyloid and tau differ. The exact relation between the beta-pleated proteins of tangles and amyloid remain poorly understood.

Amyloid beta-Peptides↗

Synaptophysin and chromogranin A immunoreactivities in senile plaques of Alzheimer's disease.

Immunolabelling for synaptophysin and chromogranin A, two polypeptides associated with small clear and large dense core synaptic vesicles respectively, has been performed on tissue sections of the temporal cortex in Alzheimer's disease in combination with anti-A4 amyloid labelling. The dystrophic neurites in many senile plaques were observed to be labelled by the anti-synaptophysin or anti-chromogranin A antibodies. Some diffuse amyloid deposits, demonstrated by antibodies against synthetic amyloid A4 peptides, were associated with a punctuate increase in synaptophysin or chromogranin A immunoreactivity. The labelling of dystrophic plaque neurites may reflect the accumulation in these processes of synaptic vesicles or material derived from them. We suggest also that the punctuate increase in synaptophysin and chromogranin A immunoreactivities associated with some A4 amyloid deposits may be an early event reflecting neuronal dysfunction.

Alzheimer Disease↗

Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site.

To investigate the extent to which whole tau proteins, structurally abnormal tau and fragments of tau are incorporated into neurofibrillary tangles in Alzheimer's disease, an immunocytochemical mapping study using a panel of antibodies to several synthetic human tau peptides has been performed. Neurofibrillary tangles were immunolabelled in situ, and paired helical filaments (PHF), the principal structural component of tangles, were immunolabelled after isolation and Pronase treatment. N-Terminal and C-terminal domains of tau were found to be present in tangles in situ. SDS-treated PHF were found to contain most of the C-terminal half of tau and were also labelled by antibodies to ubiquitin. Only some of these PHF were labelled by antisera to tau sequences towards the N-terminus, and this enabled the identification of a region of tau in which proteolytic cleavage may occur. The ultrastructural appearance of the immunolabelling suggested that both the N- and C-terminal domains of tau extend outwards from the axis of PHF. After Pronase treatment. PHF were strongly labelled only by an antiserum to PHF and by the antiserum to the most C-terminal tau synthetic peptide. The latter antiserum also strongly labelled extracellular tangles in situ, whereas these extracellular tangles were poorly labelled by the antisera to the other synthetic peptides. One anti-(tau peptide) serum labelled a population of neurofibrillary tangles in situ only after alkaline phosphatase pretreatment of tissue sections. Our results show that, although peptides along the length of the tau molecule are associated with neurofibrillary tangles in situ, only the C-terminal one-third of the molecule is tightly associated with PHF, since this region of tau is resistant to SDS treatment of PHF. We also report the existence in PHF in situ of a masked tau epitope which is partially unmasked by dephosphorylation. These results are indicative of post-translational changes in tangle-associated tau in degenerating neurons in Alzheimer's disease.

Alzheimer Disease↗

Sarcoidosis presenting as an isolated intramedullary tumor.

We report a case of isolated intramedullary sarcoidosis. The patient developed progressive signs that indicated a spinal tumor, which were investigated with contrast-enhanced magnetic resonance imaging scans. Magnetic resonance imaging clearly revealed an intramedullary lesion, but the diagnosis of sarcoidosis was made on the pathological analysis of the surgical specimen. Magnetic resonance imaging with contrast enhancement is reported in a histologically proven case of intramedullary sarcoidosis. Only 12 other cases of isolated intramedullary sarcoidosis have been reported. We review and discuss these cases according to their clinical presentation, the segmental location of the granulomas in the spinal cord, preoperative and operative diagnoses, and signs for systemic sarcoidosis. In none of the cases was the diagnosis of intramedullary sarcoidosis made before surgery. We think that surgical therapy for intramedullary lesions is the best way to diagnose rare instances of benign lesions like sarcoidosis and to treat them in an appropriate manner.

Contrast Media↗

A survey of 65 tumors within the spinal cord: surgical results and the importance of preoperative magnetic resonance imaging.

Between January 1984 and December 1990, 65 intramedullary spinal cord tumors were diagnosed and operated on. In this series, all patients underwent magnetic resonance imaging investigations and were operated on with the Cavitron ultrasonic surgical aspirator whenever necessary. Major surgical difficulties have been found in patients previously treated by radiotherapy with or without biopsy. We found magnetic resonance imaging to be a highly sensitive imaging procedure and the method of choice for visualizing tumors within the spinal cord. Nevertheless, accurate diagnosis may only be suggested by magnetic resonance imaging, rather than made definitively. Surgery is necessary in every case in order to obtain a definite diagnosis. Radical surgery can be performed when a plane exists between the tumor and the normal spinal cord: biopsy or debulking with the Cavitron ultrasonic surgical aspirator should be performed when the tumor is infiltrative. We have performed 33 so-called total resections, 22 partial resections, and 10 biopsies, among which 5 were performed on lipomas. Surgical results were assessed at 3 months after surgery, showing 35 improvements (53%), 24 stabilizations (37%), and 6 deteriorations (10%).

Adolescent↗

[Sporadic Z disk myopathy with accumulation of rods and cytoplasmic bodies].

An unusual myopathy with extensive myofibrillar degeneration related to the Z disk is reported. Focal Z disk disappearance, accumulation of numerous rods and cytoplasmic bodies and some rimmed vacuoles represented the major pathologic features of this sporadic muscular disorder, sharing common clinical and electrophysiological features with inclusion body myositis. This diagnosis was excluded because all nuclei appeared normal and 15-18 nm filaments were not observed in cytoplasm or in the vicinity of membranous whorls. Intramuscular innervation was studied by vital staining with methylene blue: the terminal innervation ratio was normal, indicating a myopathic disorder. The relationship between the present disorder and cytoplasmic bodies and nemaline myopathies is discussed.

Cytoplasmic Granules↗

Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A European multicenter study under the auspices of EURAGE.

The study reported was intended to compare the impressions and analyses of investigators from 11 different laboratories on 2 slides, each from 6 cases with varying quantities of neuropathological change of the type found in Alzheimer's disease and normal ageing. The material came from 6 selected female patients over 75 years of age all of whom had been examined in detail and assessed by the Blessed Test Score. Two were severely demented, 2 mildly demented and 2 were considered to be normal. Unstained paraffin-embedded slides were sent to the investigators, the choice of the staining techniques being left to each laboratory. A quantitative evaluation of the changes was requested in 2 specified areas of the hippocampus and in the first temporal gyrus. Subjective scores of severity and a final guess about the pre mortem intellectual status (demented or not) were asked. The 11 replies were analyzed. A total of 14 different staining techniques were used. Absolute values of density differed much from one investigator to another, for senile plaques as well as for neurofibrillary tangles. Statistical analysis showed that concordance might be improved by the use of corrective factors which would standardize the scales of measurement. The ranking of the slides in increasing order of severity was in good agreement for 9 out of 11 observers concerning the neurofibrillary tangles and 3 out of 9 observers concerning the senile plaques. The correlation between the intellectual status and the density of lesions was higher for neurofibrillary tangles than for senile plaques. The subjective scores were in better agreement for the severely affected cases than for the mildly affected ones. The lowest correlation with intellectual deficit was obtained with the quantitative scores which took into account only the senile plaques or only the hippocampal lesions. The highest correlation coefficients were obtained with the subjective scores. The observers guessed correctly the intellectual status of the 2 most affected cases and often disagreed for the intermediate and normal cases. Neuropathology is mandatory for the diagnosis of definite Alzheimer's disease. Quantitative assessment is useful in cases with few lesions and light dementia but the neuropathological diagnostic procedure has to be more strictly standardized before quantitative histopathological criteria can be reliably transferred from one laboratory to another, especially when mildly affected cases are involved. Concordance seems presently easier to obtain by ranking the lesions and the cases in increasing order of severity than by using quantitative values of density.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Paraganglioma of the cauda equina. Report of 2 cases and review of 59 cases from the literature.

Paragangliomas of the cauda equina are not so rare as said in the literature. Two additional cases are presented with a global analysis of the 59 cases from the literature. The diagnosis of this pathology greatly benefit of the use of immunostainings as the cells are often neuron-specific enolase, neurofilament protein and somatostatin positive so that electron microscopy is thus no longer mandatory for establishing the diagnosis. In addition, we report the first magnetic resonance images of this tumor at this location.

Adult↗

Lung fibrosis induced by Thorotrast.

A 63 year old woman developed progressive shortness of breath, pulmonary hypertension, and respiratory failure and died from pulmonary fibrosis 45 years after thoracic fistulography with Thorotrast. Bouts of acute respiratory failure occurred with features of noncardiogenic pulmonary oedema. Lung tissue obtained by biopsy and at necropsy showed abundant radioactive particles of thorium dioxide in the lungs. The particles were congregated in the walls of blood vessels and in perivascular fibrous zones, consistent with a causal role of Thorotrast in the development of lung fibrosis. It is suggested that the fibrosis was due to the combined effects of alpha radiation on the interstitial perivascular zones and of recurrent pulmonary oedema due to endothelial damage.

Autoradiography↗