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Biomedical subjects

M M Ruchoux

Publications and source records attributed to M M Ruchoux.

At least 55 records · Page 3Linked to original sources
PubMed1997

Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype.

The hypothesis that tumor growth is angiogenesis dependent has been documented by a considerable body of direct and indirect experimental data. A prerequisite for the development of novel anti-angiogenic agents is the design of drugs that would be active only on those endothelial cells with an angiogenic phenotype. We took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for the vascular endothelial growth factor receptor KDR/flk-1 (J-IgG). They induced in the absence of VEGF cell proliferation in vitro and angiogenesis in the corneal pocket assay either through local or systemic delivery. Intraperitoneal injections of J-IgG in nude mice grafted with a prostatic adenocarcinoma led to tumor enlargement associated with an increase in both tumor vascularization and proliferation. In contrast KDR/flk-1 overstimulation had no detectable effect on normal tissues. These data underline that KDR/flk-1 is a functional marker of the angiogenic phenotype of endothelial cells.

Adenocarcinoma↗
PubMed1996

Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia.

Stroke is the third leading cause of death, and vascular dementia the second cause of dementia after Alzheimer's disease. CADASIL (for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) causes a type of stroke and dementia whose key features include recurrent subcortical ischaemic events and vascular dementia and which is associated with diffuse white-matter abnormalities on neuroimaging. Pathological examination reveals multiple small, deep cerebral infarcts, a leukoencephalopathy, and a non-atherosclerotic, non-amyloid angiopathy involving mainly the small cerebral arteries. Severe alterations of vascular smooth-muscle cells are evident on ultrastructural analysis. We have previously mapped the mutant gene to chromosome 19. Here we report the characterization of the human Notch3 gene which we mapped to the CADASIL critical region. We have identified mutations in CADASIL patients that cause serious disruption of this gene, indicating that Notch3 could be the defective protein in CADASIL patients.

Adult↗
PubMed1996

Specific tau variants in the brains of patients with myotonic dystrophy.

The mutation causing myotonic dystrophy (DM) is an unstable CTG trinucleotide repeat in a gene encoding for a protein with putative serine-threonine kinase activity. Several studies have reported the appearance of abnormally frequent neurofibrillary tangles (NFTs) in the cortex of patients with DM. Using immunologic probes against normal and pathologic hyperphosphorylated tau proteins, the basic components of NFTs, we performed a biochemical and immunohistochemical study of the brains of two DM cases. We compared the tau profiles with those found in Alzheimer's disease (AD) using mono- and two-dimensional immunoblotting. Patients were aged 53 and 61 years at death. In both cases, we observed few perikaryal and axonal inclusions in the hippocampus as well as the entorhinal and inferior temporal cortices. As in AD brain homogenates, pathologic tau proteins, named tau 55, 64, and 69, were exclusively immunodetected in the DM cases in the hippocampus, the entorhinal cortex, and in most of the temporal areas. Amounts of pathologic tau proteins were higher in the more severely affected case, but lower than in AD brain homogenates. Pathologic tau proteins were less acidic in DM than in AD. We found a very low amount of the tau 69 isoform in DM extracts, and in most of the cortical areas, tau 55 was overexpressed compared with AD homogenates. A link between the increase of kinase activity and the presence of pathologic tau proteins is discussed.

Brain↗
PubMed1996

[MRI aspect and course of supra-tentorial sarcoidosic lesions].

Central nervous system lesions resulting from sarcoidosis occur in 5% of cases, but supratentorial mass lesions are uncommon. We report 3 cases of intracranial pseudo-tumoral lesions, due to sarcoidosis: 1 woman and 2 men. Clinical features included left facial myoclonus, headache and vertigo, right hemiparesis and unique general seizure. Sarcoidosis was diagnosed upon conjonctival biopsy in the first case, infiltrative lesions of the lungs and mediastinal lymph nodes in the second case, and intracerebral lesion plus lymph nodes biopsies in the last case. In the first case, CT scan and MRI images showed diffuse subcortical high signal, suggesting pachymeningitis with vasogenic oedema. In the second case, GT scan and MRI revealed numerous small granuloma in the left rolandic area, and one in the striatum. In the third case, CT scan showed an enlargement of the left temporal horn, due to an enhanced left periventricular lesion. MRI with gadolinium showed that the lesion encircled the ventricle horn. In all cases, clinical and radiological improvement was obtained after corticoid therapy.

Adult↗
PubMed1996

[Modulation of the tumoral progression by anti-idiotypic antibodies of angiogenesis factors].

We took advantage of the anti-idiotypic strategy to design circulating probes mimicking the biological effects of VEGF (vascular endothelial growth factor) or FGF2 (fibroblast growth factor 2). The activation of the VEGF receptor KDR/flk-1 induced endothelial cell proliferation but not their migration, whereas that of the FGF receptor FGF-R1 gave opposite results. The long lasting delivery of KDR/flk-1 agonists, but not that of FGF-R1, in nude mice grafted with tumor fragments enhanced the tumor volume. Microscopic examination showed an increase in both the vascularization and the proliferation of cancer cells. In contrast, no difference in cell proliferation was observed within normal tissues.

Adenocarcinoma↗
PubMed1996

[MRI and computer-assisted tomography in Kufs disease. Apropos of a familial form].

Kufs disease is the adult form of ceroid neurolipofuscinosis, and an uncommon cause of degenerative nervous system disease affecting young adults. We present here 4 cases of family form revealed by a demential syndrome. In all 4 patients MRI showed diffuse cortical atrophy predominant in the parietal regions. In 3 of these 4 patients MRI also exhibited a low signal in T2-weighted sequences on the putamens. There was no abnormality of the white matter. Diagnosis was made by cerebral biopsy in one case and by rectal biopsy in all other cases. Although the MRI images are not specific, they must be used when the diagnosis of Kufs disease is suspected in young patients with demential syndrome.

Adult↗
PubMed1995

Developmental aspects of type II lissencephaly. Comparative study of dysplastic lesions in fetal and post-natal brains.

We report neuropathological studies of five cases of type II lissencephaly from three fetuses and two infants. This comparative study allowed us to determine the developmental course of the cerebral lesions. Two distinct developmental events seem to generate this type of brain malformation: firstly, an early disturbance in cortex formation, which results both from a disorder of radial migration and a pial barrier disruption; secondly, a late perturbation of cerebral surface organization, resulting in fusion of the cerebral surface. All these features can be related to a primitive meningeal pathology, and more generally, to a neurocristopathy. Accordingly to our observations, this brain malformation appears during both migrational and post-migrational stages and may be considered more like a polymicrogyria than a lissencephaly.

Abnormalities, Multiple↗
PubMed1995

Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by a cerebral non-atherosclerotic, nonamyloid angiopathy mainly affecting the small arteries penetrating the white matter. In the brain vessels of two patients with CADASIL, abnormal patches of granular osmiophilic material have recently been described. Here we report the observation of similar granular osmiophilic material within the vessel walls of muscle and skin biopsies from a 54-year-old woman belonging to a CADASIL family, who suffered from subcortical dementia with leukoencephalopathy demonstrated on neuroimaging. Postmortem examination disclosed changes of the vessel walls in all the organs chiefly leading to cerebral lesions. Ultrastructural study showed destruction of the vascular smooth muscle cells (VSMC) and the granular osmiophilic material already found in muscle and skin biopsies in this patient. Both changes were found all along the arterial tree. The findings of this study indicate that CADASIL is a systemic vascular disease involving arterial VSMC and that the lesions are different in each organ and vessel wall, depending on their fine structure. Moreover, it emphasizes that skin and muscle biopsies might be useful for diagnosis of and research into CADASIL.

Brain↗
PubMed1995

Carcinomatous meningitis in a case of anaplastic meningioma.

Malignant meningiomas are associated with a high rate of local recurrence, but seldom give remote metastases. Here, we report a case with carcinomatous meningitis occurring 13 months after treatment of the initial tumor. MRI showed no significant abnormalities. CSF contained abnormal cells, and electronic microscopy after cytocentrifugation confirmed their identity with the initial tumor.

Adult↗
PubMed1995

[Nervous microangiopathy and POEMS syndrome].

The authors report the case of a 40 year-old man with POEMS syndrome (peripheral neuropathy, organomegaly, endocrinopathy, M-protein and skin changes). Pathological studies of the peroneal nerve showed a microangiopathy of the vasa nervorum. Several authors have already reported microvascular abnormalities that could be responsible for some systemic manifestations of the POEMS syndrome, involving the skin, the kidney and the peripheral nerves. This new case enhances this hypothesis. The relation between microangiopathy and plasma cell dyscrasia is unknown.

Adult↗
PubMed1995

[Demonstration of a specific profile of pathological Tau proteins in frontotemporal dementia cases].

We compared samples of different brain areas from patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), controls subjects and from 4 patients who met the clinical and pathological criteria for frontotemporal dementia (FTD), using a Western blot analysis. We used polyclonal antibodies directed against Tau proteins and the monoclonal antibody AD2 for the immunodetection of the pathological Tau proteins which are the basic components of neurofibrillary degeneration. In the PSP and AD cases, we respectively detected the abnormal Tau proteins 64 and 69 and the Tau proteins 55, 64, and 69, systematically associated with bands and smears, corresponding to catabolic products or aggregates of these abnormal Tau proteins. In FTD cases, the abnormal Tau proteins 55, 64 and 69 were also detected in the frontal and temporal poles from the autopsied case and in the cortical biopsies. However, the profiles were different because smears and proteolytics products of Tau proteins were absent. There was no detection of abnormal Tau proteins in control brain homogenates and in biopsies from patients with other neurodegenerative disorders such as spongiform encephalopathies or primitive gliosis. These results demonstrate that pathological Tau proteins are produced during FTD degenerating process, despite the absence of neurofibrillary lesions.

Adult↗
PubMed1994

Uncompacted myelin lamellae in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome. Ultrastructural study of peripheral nerve biopsy from 22 patients.

Mechanisms of peripheral neuropathies in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome are poorly understood. A peripheral nerve biopsy was performed in 22 patients. Of these 9 had histological features of Castleman's disease on lymph node biopsies, and 19 had a monoclonal lambda light chain in their serum. Certain nerve fragments were paraffin embedded, others were frozen and studied by direct immunofluorescence, and others were fixed for ultrastructural examination. Paraffin-embedded fragments did not show any amyloid deposits, and at direct immunofluorescence there was no immunoglobulin fixation. At ultrastructural examination, features of uncompacted myelin lamellae (UML) were present in 19 patients, and their frequency varied from 1% to 16% of myelinated fibres. Up to now UML have been reported only in 7 patients with POEMS syndrome in the literature. UML have also been noticed in a few cases of inflammatory demyelinating polyradiculoneuritis and inherited tendency to pressure palsy.

Aged↗
PubMed1994

Long-term thalamic stimulation in Parkinson's disease: postmortem anatomoclinical study.

Parkinsonian tremor may be suppressed by thalamic stimulation. For an equivalent clinical efficacy, its obvious advantage over micro-thalamotomy is its reversibility. This patient experienced postural tremor at the age of 44 years and akineto-rigid syndrome 8 years later. At the age of 60 years, intrathalamic stimulation was applied over a long-term period of 43 months until death and was efficient on tremor with low stimulation. This case is the first with anatomic verification. The extent of the lesion provoked by the electrode is very small. The location of the stimulation site was in the medio-inferior part of the intermedius complex at the entrance of cerebello-thalamic fibers. The stimulation of the cerebellar afferent axons could be the cause of the clinical effect. The stimulation site corresponds to the thalamic source of the precentral and accessory motor cortex, which correlates with changes observed in our PET study showing a regional cerebral blood flow decrease in cerebellar nuclei and also in precentral and accessory motor cortex. The places and mechanisms of the effects of stimulations and lesions could be different.

Adult↗