Biomedical subjects

Catherine Daumas-Duport

Publications and source records attributed to Catherine Daumas-Duport.

5 recordsLinked to original sources

PubMed2005

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier.

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a two-compartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r = 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.

Algorithms↗

PubMed2004

Diffusion tensor imaging of partial intractable epilepsy.

Our aim was to assess the value of diffusion tensor imaging (DTI) in patients with partial intractable epilepsy. We used DTI (25 non-collinear directions) in 15 patients with a cortical lesion on conventional MRI. Fractional anisotropy (FA) was measured in the internal capsule, and in the normal-appearing white matter (WM), adjacent to the lesion, and away from the lesion, at a set distance of 2-3 cm. In each patient, increased or decreased FA measurements were those that varied from mirror values using an arbitrary 10% threshold. Over the whole population, ipsi- and contralateral FA measurements were also compared using a Wilcoxon test (p<0.05). Over the whole population, FA was significantly reduced in the WM adjacent to and away from the lesion, whilst being normal in the internal capsule. FA was reduced by more than 10% in the WM adjacent to and distant from the lesion in 13 and 12 patients respectively. For nine of the ten patients for whom the surgical resection encompassed the limits of the lesion on conventional MRI, histological data showed WM alterations (gliosis, axonal loss, abnormal cells). DTI often reveals WM abnormalities that are undetected on conventional MRI in patients with partial intractable epilepsy.

Adolescent↗

PubMed2004

New variants of malignant glioneuronal tumors: a clinicopathological study of 40 cases.

OBJECTIVE: To demonstrate that malignant glioneuronal tumors comprise a large spectrum of neoplasms, without mature ganglion-like cells, that may histologically resemble any malignant glioma (World Health Organization Grade III or IV) but have a distinct biological behavior. METHODS: This series includes all tumors diagnosed as malignant glioneuronal tumors (MGNTs) in our routine practice during a 2-year period during which neurofilament protein (NFP) immunostaining was performed in any case of suspected malignant glioma with unusual clinical, radiographic, and/or histological features. Immunostaining using neuronal markers (NFP, NeuN, synaptophysin, and chromogranin) and glial fibrillary acidic protein was done on paraffin sections after antigen retrieval. The presence of NFP-positive tumor cells, including those in mitosis, was used as a hallmark diagnostic criterion of MGNT. RESULTS: All tumors coexpressed glial fibrillary acidic protein and NFP. Other neuronal markers tested were inconstantly expressed. No recurrence was observed at the primary site in 36.4% of patients who underwent gross total resection. Twelve patients (33.3%) developed intra-axial and/or systemic metastases, and 4 were free of disease at 39 to 184 months. Univariate analysis revealed that gross total surgical resection was the most important prognostic factor predicting survival (44 versus 15 mo; P < 0.0001), followed by a long duration of symptoms (>1 yr; P = 0.005), young age at symptom onset (children versus adults; P = 0.045), and absence of necrosis (P = 0.02). Gross total surgical resection (P = 0.001) and a long duration of symptoms (symptoms > 1 yr; P = 0.013) proved to be independent and statistically significant prognostic factors in the multivariate analysis. CONCLUSION: NFP immunostaining is required to identify MGNTs accurately. Their distinction from malignant gliomas is of paramount clinical importance, particularly for neurosurgeons, because gross total surgical resection may be curative in some cases. Finally, MGNTs may account for the long-term survival and/or occurrence of metastases demonstrated in a subset of malignant gliomas.

Adolescent↗

PubMed2003

Synemin expression in developing normal and pathological human retina and lens.

Synemin (Syn) is an intermediate filament (IF) protein. To gain insight into a morphogenetic role of Syn, we have studied its expression patterns in the developing human retina and lens and compared it with those of other IF proteins. In addition, we have tested Syn expression in fetuses (23 and 28 weeks) affected by Walker-Warburg syndrome (WWS), Meckel syndrome, and trisomy 13. In the retina, Syn expression starts in the nerve fiber and ganglion cell layers (NFL and GCL) at 15 weeks, remains there in up to 20 weeks, and spreads to other layers and may be colocalized with vimentin, GFA, or neurofilaments in the subsequent 16 weeks. This expansion of Synemin expression from 20 to 28 weeks is not observed in WWS in which Syn immunoreactivity in NFL is reduced and Vim expression is increased. Changes are seen in Syn or vimentin expressions in the retinae of 23-week-old Meckel syndrome or 28-week-old trisomy 13 fetuses. Syn expression in the lens is, at first (16 weeks), uniformly distributed, becoming stronger in the epithelium of the anterior part at 25 weeks and later. As in the retina, Syn expression in lens is also selectively affected in WWS. The colocalization of Synemin with vimentin, GFA, or NF supports the idea that Syn is a key cross-linking protein that connects different cytoskeletal structures. Moreover, stagnant Syn expression in WWS retina and lens reinforces the notion of a significant role of this protein in morphogenesis.

Fetal Diseases↗

PubMed2002

Immunohistological localization of the myelinating cell-specific receptor LP(A1).

LP(A1) (also termed Edg-2 or VZG-1) is a G-protein-coupled receptor for lysophosphatidic acid and its gene transcripts have been found selectively expressed by mature myelin-producing cells. We have raised in rabbit a polyclonal antibody against a sequence unique to LP(A1) and common to rat, mouse, and human orthologues. In Western blots, LP(A1) immunoreactivity appeared as 44-53 kDa bands in extracts from recombinant RH7777 cells expressing LP(A1), mouse purified oligodendrocytes, or human white matter, but not from wild-type RH7777 cells or purified astrocytes. In glial cultures, LP(A1) immunoreactivity was restricted to oligodendrocytes, appeared at cell membrane and processes, colocalized with myelin basic protein, and appeared before myelin/oligodendrocyte glycoprotein. In slices of rat and human brains, LP(A1) immunoreactivity was found in myelinated tracts, as well as in oligodendrocyte somata and their myelinating fibers. Immunoreactivities of LP(A1) and myelin basic protein colocalized in the brain, but oligodendrocyte soma showed stronger signals for LP(A1) than myelinated fibers, whereas the reverse was true for myelin basic protein. These results strengthen the view that LP(A1) is involved in myelin formation or maintenance.

Animals↗