PubMed Health⌕ Search

Biomedical subjects

M M Ruchoux

Publications and source records attributed to M M Ruchoux.

At least 19 recordsLinked to original sources
PubMed2001

Short stature, abnormal face, joint laxity, dislocation, hernias, delayed bone age, and severe psychomotor retardation in two brothers: previously undescribed MCA/MR syndrome.

We describe two brothers with severe psychomotor retardation, short stature, microbrachycephaly, flat occiput, ptosis, low set and prominent ears, "beaked" nose, joint hyperlaxity and dislocation, hernias, delayed bone age, and abnormalities on skin biopsy. Their parents are first cousins. To the best of our knowledge, this syndrome has not been reported before.

Abnormalities, Multiple↗
PubMed2001

Lactoferrin is synthesized by activated microglia in the human substantia nigra and its synthesis by the human microglial CHME cell line is upregulated by tumor necrosis factor alpha or 1-methyl-4-phenylpyridinium treatment.

The presence of the iron-binding protein lactoferrin (Lf) in some specific areas of the central nervous system and particularly in the normal human substantia nigra, where it is found in dopaminergic (DA) neurons and some glial cells, led us to investigate Lf synthesis in this area. Lf mRNA were identified using in situ hybridization and found in small ameboid cells. These cells were identified using immunocytochemistry as activated microglia since they exhibited macrophage markers such as the CD68 and the CR1 antigens. Double immunofluorescent labeling confirmed that the two Lf immunostained cell populations were activated microglia and DA neurons. Since activated microglia contained both Lf and its messenger, these cells are the Lf producing cells. The presence of Lf in DA neurons in which no Lf messengers were visible, might be due to an endocytosis mechanism, DA neurons probably internalizing Lf produced in microglial cells located in their neighborhood. In neuropathological disorders, such as Alzheimer's and Parkinson's diseases, inflammatory process and oxidative stress are events that contribute to neuronal death. Since Lf concentration increases during these pathologies, we studied the level of Lf expression under these different stresses and showed, using RT-PCR, that the immortalized human embryonic microglial CHME cell line produced Lf transcripts under tumor necrosis factor alpha or 1-methyl-4-phenylpyridinium treatment whereas untreated cells did not. These data confirm that Lf is produced only when microglia are activated.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Paradoxical phosphorylation of the serine 199 on tau proteins from young individuals.

The microtubule-associated tau proteins are abnormally aggregated in many tauopathies. Phosphorylation modulates the functions of tau. The serine 199 residue of tau is abnormally phosphorylated at early and late stages of Alzheimer's disease. The presence of the phosphorylated Ser199 was investigated in autopsy-derived and biopsy-derived brain tissue samples from non-demented individuals. A paradoxical expression was found in the hippocampus of the youngest ones, in granule cells of the dentate gyrus and in pyramidal cells of the Ammon's horn, which are particularly prone to neurodegeneration in several tauopathies. The rate of positive cells decreased with age. These data emphasize the importance of the phosphorylation of the Ser199 residue of tau in ageing and susceptibility to neurodegeneration.

Adolescent↗
PubMed2001

New autosomal recessive cerebellar ataxia disorder in a large inbred Lebanese family.

A large inbred Lebanese pedigree with congenital spastic ataxia, microcephaly, optic atrophy, short stature, speech defect, abnormal osmiophilic pattern of skin vessels, cerebellar atrophy, and severe mental retardation transmitted as an autosomal recessive trait has been studied. None of the children had any evidence of a metabolic disease, and the analysis of respiratory chain complex abnormalities was unremarkable. Only one child had a history of perinatal difficulties. Differential diagnosis and the possibility that this disorder is a hitherto unreported one are discussed.

Adolescent↗
PubMed2001

Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma.

Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.

Adult↗
PubMed2001

Melanotic neuroectodermal tumour of the pineal region.

We describe CT and MR findings in a 23-month-old infant with a melanotic neuroectodermal tumour of the pineal gland. The tumour has been stereotactically biopsied and surgically resected. The pathological diagnosis was made on the resected piece. Embryology of the pineal gland and the histology of melanotic neuroectodermal tumour of infancy are discussed.

Brain Neoplasms↗
PubMed2001

Cerebellar gliomas in infants: specificity, pathology, and outcome.

Cerebellar gliomas (CGs) in children are generally associated with a favorable outcome; however, data regarding these tumors in very young children are scarce. We report on our experience with CGs in children less than 3 years old at surgery, compared with a second group older than 3 years. From 1991 to 1996, we operated on 7 children with CGs in the first group and 43 in the second. Psychomotor delay and regression were the first symptoms in 3 cases, and 3 had macrocrania. The tumor was totally removed in all cases. One child died intraoperatively of air embolism and subdural bleeding. Three had malignant tumors (grade 3 or 4). There was no operative mortality or malignancy in the second group of patients. With a mean follow-up of 33 months, all survivors in the first group are disease-free, with no or minimal symptoms, and attend normal schools. The clinical, surgical, and pathological features suggest that children under 3 years of age represent a specific subgroup of CGs.

Adolescent↗
PubMed2001

Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration.

Galectins, a family of mammalian lectins with specificity to beta-galactosides, are involved in growth-regulatory mechanisms and cell adhesion. A relationship is assumed to exist between the levels of expression of galectins and the level of malignancy in human gliomas. A comparative study of this aspect in the same series of clinical samples is required to prove this hypothesis. Using computer-assisted microscopy, we quantitatively characterized by immunohistochemistry the levels of expression of galectins-1, -3 and -8 in 116 human astrocytic tumors of grades I to IV. Extent of transcription of galectins-1, -3, and -8 genes was investigated in 8 human glioblastoma cell lines by means of RT-PCR techniques. Three of these cell lines were grafted into the brains of nude mice in order to characterize in vivo the galectins-1, -3 and -8 expression in relation to the patterns of the tumor invasion of the brain. The role of galectin-1, -3 and -8 in tumor astrocyte migration was quantitatively determined in vitro by means of computer-assisted phase-contrast videomicroscopy. The data indicate that the levels of galectin-1 and galectin-3 expression significantly change during the progression of malignancy in human astrocytic tumors, while that of galectin-8 remains unchanged. These three galectins are involved in tumor astrocyte invasion of the brain parenchyma since their levels of expression are higher in the invasive parts of xenografted glioblastomas than in their less invasive parts. Galectin-3, galectin-1, and to a lesser extent galectin-8, markedly stimulate glioblastoma cell migration in vitro. Since bands for the transcripts of human galectins-2, -4 and -9 were apparently less frequent and intense in the 8 human glioblastoma cell lines, this system provides an excellent model to assign defined roles to individual galectins and delineate overlapping and distinct functional aspects.

Adolescent↗
PubMed2001

Supratentorial ependymoma in children.

The clinical and pathological characteristics of supratentorial ependymomas (STE) in children are not well identified in the literature, because most series deal with ependymomas regardless of their location or the age of the patient. As a result, the pathological description of the disorder is still debated. We therefore reviewed our cases of children operated for STE and compared them with cases of infratentorial ependymomas (ITE) to provide a better characterization of STE and suggest guidelines for treatment. From 1985 to 1999, we operated 18 children for STE, almost half of which developed with no connection to the ventricular system. Intraoperative bleeding and infiltration of the basal ganglia prevented total removal in 4 cases and were the main causes of operative mortality and morbidity. The 5-year overall survival and recurrence-free survival rates were 54 and 37%, respectively, and were highly affected by the extent of resection, but not by histological grade. Because of the high recurrence rate, we recommend systematic postoperative irradiation limited to the tumor site for all high-grade tumors in older children, and reoperation after subtotal removal and for recurrences.

Adolescent↗
PubMed2001

[Cerebellar pilocytic astrocytomas in children. Report of 72 cases].

BACKGROUND AND PURPOSE: Cerebellar pilocytic astrocytoma (CPA) bears a well-deserved reputation of benignity. However, these tumors infiltrate the brainstem in a number of cases, and total removal may cause morbidity, whereas subtotal removal can lead to recurrence. MATERIAL AND METHODS: To define guidelines for tumor removal, management of tumor remnants and recurrence, we reviewed 72 cases of CPA of childhood operated on in our department since the introduction of CT. RESULTS: Surgical removal was total in 57 cases, had to be withheld because of brainstem infiltration in nine cases, and was revealed subtotal by postoperative imaging in six cases. Two of the latter were reoperated on; six had only radiological controls and did not progress. Early in the series, eight children had external irradiation because of subtotal removal or recurrence. Three children were reoperated on for tumor recurrence, between six and eight years after complete removal. We had no tumor-related mortality; long-term disability could be related to previous mental retardation, the severity of clinical state at presentation, and complications of surgery and irradiation. CONCLUSION: The goal of surgery is to cure the patient with minimal morbidity, however, total removal is not always possible. In our experience: i) tumor remnants can be surveyed radiologically, and reoperated only in case of progression; ii) the indications for radiotherapy should be the exception; iii) clinical and radiological follow-up should be protracted beyond entry into adulthood.

Adolescent↗
PubMed2000

Cerebellar gliomas in children with NF1: pathology and surgery.

Cerebellar gliomas associated with NF1 (CGNF1) are rarely reported in the literature, and they are considered to be malignant in a high proportion of cases. In an attempt to improve the definition of this disease and clarify its management, we reviewed our patients with CGNF1 and compared their tumors with sporadic cerebellar gliomas (SGC). We operated on six children with CGNF1, all but one of whom were asymptomatic. They represented one-tenth of all pediatric cerebellar gliomas, and one third of NF1-associated gliomas seen in our institution. CGNF1 appeared at a later age than SCG. They are seated near the roof of the IV ventricle and are not related to white matter hypersignal hamartomas. Most of these tumors showed radiological progression. They were four pilocytic astrocytomas, one ganglioglioma, and one malignant astrocytoma. One patient had tumor recurrence after 8 years, and the others are still disease free. The overall outcome appeared to be better for GCNF1 than for SCG. On account of the regular growth, uncertain pathology, and good surgical outcome, we advocate systematic resection of these tumors.

Adolescent↗
PubMed2000

Skin biopsy value and leukoaraiosis.

In the field of leukoaraiosis, the identification of CADASIL and its link to Notch 3 mutation has shed light on the pathogenesis of white matter (WM) abnormalities related to small-vessel disease. Since 1993, its systemic vascular involvement allows skin biopsy diagnosis and research on tissues before postmortem examination. We received 160 skin biopsies from patients presenting subcortical dementia, recurrent strokes, behavioral disturbances or migraines, and suspected CADASIL. Almost all the patients lacked the well-known vascular risk factors. The ultrastructural study was systematically carried out looking at the vessel walls and the other components found in skin. In a third, we found endothelial changes, destruction of vascular smooth muscle cells (VSMCs), and characteristic granular osmiophilic material (GOM). In these cases, the genetic analysis confirmed the Notch 3 mutation. Curiously, the skin biopsies from the other two thirds presented marked alterations within the vessel walls. Such changes included destruction of VSMCs, lack of GOM, and replacement of these cells by an extracellular matrix. Frequently, we noticed endothelial pathological changes as well as other tissue impairments. By now, we are able to describe eight different groups of lesions according to either the prevalence of a lesion or the association of different lesions. The skin biopsy ultrastructural study seems to be highly informative given that we can observe vessel lesions and association of impairments in various tissues that might, in part, explain the brain vessel involvement and then the leukoaraiosis and probably some clinical symptoms. Moreover, these vessel lesions often belonged to young people (30-50 years old), and many of them seemed to run in families. These new data associated with early onset of clinical symptoms and leukoaraiosis would be extremely valuable in clarifying the wide field of leucoencephalopathy and might provide genetic research with new issues.

Adult↗
PubMed2000

Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases.

The WHO classification of CNS tumors divides pineal parenchymal tumors (PPT) into pineocytoma (PC), pineoblastoma (PB) and mixed pineocytoma-pineoblastoma or PPT with intermediate differentiation. The reported incidence of mixed/intermediate PPT varies and this may reflect the difficulty in classifying tumors of this type. In an attempt to overcome the problem of the classification of PPT with intermediate differentiation, we describe the relationship between histological features and patient survival in a large cooperative series of 66 PPT from 12 neurosurgical centres. All tumors were studied with both light microscopy and immunohistochemically using antibodies against glial markers or neural/neuroendocrine markers. Our series included 11 PC, 39 mixed/intermediate PPT and 16 PB. A number of mitoses greater than 6 and the presence of necrosis were associated with a poorer outcome, while positive immunostaining for neurofilaments was associated with a better survival. We propose a new prognostic grading of 4 grades, grade I for PC, grade II for PPT with fewer than 6 mitoses and positive immunolabelling for neurofilaments, grade III for PPT with either 6 or more than 6 mitoses or fewer than 6 mitoses but without immunostaining for neurofilaments and grade IV for PB.

Adolescent↗
PubMed1999

Simultaneous presentation of atypical teratoid/rhabdoid tumor in siblings.

Atypical rhabdoid/teratoid tumor (ATT/RHT) is a rare malignant neoplasm which appears in early childhood. The present paper describes clinical and pathological features of ATT/RHT which occurred simultaneously in 2 sisters diagnosed at a 15 day interval. Both children were treated by surgical resection, subtotal in the first case and total in the second. Postoperatively, chemotherapy followed by radiotherapy, 50.4 Gy on the posterior fossa, were administered. Despite this therapy, both sisters died at 14 months and 26 months respectively. The tumors express vimentin and EMA; cells contained intracytoplasmic inclusions. No karyotypic anomaly was detected. This is the first description of familial ATT/RHT.

Brain Neoplasms↗
PubMed1999

Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins.

The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.

Adolescent↗
PubMed1999

[Angiogenesis and neuropathology].

Angiogenesis is crucial for both tissue development and tissue function and is an integral part of central nervous system embryogenesis and tumor growth. Angiogenesis is extremely active during development, then remains stable during adulthood and decreases gradually during aging. Physiological processes and inflammation can transiently stimulate angiogenesis in adults. Angiogenesis is modulated by a host signaling pathways, growth factors, growth factor receptors, and membrane proteins associated with these receptors or transcription factors. In disorders affecting the central nervous systems, as in those arising elsewhere in the body, angiogenesis can become inadequate, excessive, or qualitatively abnormal (dysplasia). These abnormalities can result in cerebral trophic disorders and in secondary remodeling. A few examples are given to illustrate various types of primary angiogenesis disorders responsible for cerebral lesions and of secondary angiogenesis disorders caused by an underlying cerebral disorder.

Adult↗