Biomedical subjects

N Baumann

Publications and source records attributed to N Baumann.

At least 19 recordsLinked to original sources

PubMed1997

Localized proton magnetic resonance spectroscopy in patients with adult adrenoleukodystrophy. Increase of choline compounds in normal appearing white matter.

OBJECTIVES: To describe the changes in the results of magnetic resonance imaging and spectroscopy occurring in the normal-appearing white matter of patients with adult adrenoleukodystrophy and to present evidence of a particular change that may serve as a marker for the follow-up of the disease. DESIGN: Neurologic, magnetic resonance imaging, and localized proton spectroscopic examinations were performed in 11 patients with adult adrenoleukodystrophy and compared with 11 sex- and age-matched controls. PATIENTS: Eleven patients with adult adrenoleukodystrophy participated in a trial of dietary therapy with glyceryl trioleate and glyceryl trierucate (Lorenzo's oil) in the Fédération de Neurologie and the Institut National de la Santé et de la Recherche Médicale, Unité 134, at the Hôpital de la Salpêtrière in Paris, France. RESULTS: The results of magnetic resonance imaging of the white matter were normal in 2 patients and showed areas of mild symmetrical hypersignals on T2-weighted images and fluid attenuated inversion recovery sequences, localized in the posterior white matter in 9 patients. The results of spectroscopy indicated that the peak of the area of choline-containing compounds was increased at long echo times in patients with adult adrenoleukodystrophy, which may reflect very long-chain fatty acid accumulation in this disease. The peak of the area of myo-inositol-containing compounds was increased at short echo times in patients with adult adrenoleukodystrophy, which may indicate a rise in this metabolite concentration. The N-acetylaspartate-creatine amplitude ratio was significantly decreased in patients with motor deficit. The significance of this finding remains to be established. CONCLUSIONS: The results of localized proton magnetic resonance spectroscopy show abnormalities in the cerebral white matter of patients with adult adrenoleukodystrophy, which may contribute to the understanding of the pathophysiologic characteristics of the disease. Although changes in the results of spectroscopy found in this disease are not specific, the increase of choline-containing compounds may reflect the accumulation of very long-chain fatty acids in the central nervous system. Localized proton magnetic resonance spectroscopy may prove a valuable technique, in addition to magnetic resonance imaging, for noninvasive investigation of patients with adult adrenoleukodystrophy undergoing future clinical trials.

Adrenoleukodystrophy↗

PubMed1997

Juvenile-onset spinal muscular atrophy caused by compound heterozygosity for mutations in the HEXA gene.

Progressive proximal muscle weakness is present both in spinal muscular atrophy (SMA) type III (Kugelberg-Welander disease) and in GM2 gangliosidosis, diseases that segregate in an autosomal recessive fashion. The SMN gene for SMA and the HEXA gene for GM2 gangliosidosis were investigated in a woman with progressive proximal muscle weakness, long believed to be SMA type III (Kugelberg-Welander type). She and her family underwent biochemical studies for GM2 gangliosidosis. Analysis of SMN excluded SMA. Biochemical studies on GM2 gangliosidosis showed deficiency in hexosaminidase A activity and increased GM2 ganglioside accumulation in the patient's fibroblasts. The HEXA gene was first analyzed for the Gly269-->Ser mutation characteristic for adult GM2 gangliosidosis. Since the patient was carrying the adult mutation heterozygously, all 14 exons and adjacent intron sequences were analyzed. A novel mutation in exon 1 resulting in an A-to-T change in the initiation codon (ATG to TTG) was identified. The adult patient is a compound heterozygote, with each allele containing a different mutation. Although mRNA was transcribed from the novel mutant allele, expression experiments showed no enzyme activity, suggesting that neither the TTG nor an alternative codon serve as an initiation codon in the HEXA gene.

Adult↗

PubMed1996

Membrane glycolipids and human immunodeficiency virus infection of primary macrophages.

The membrane glycolipids galactosylceramide (GalCer) and sulfatide (SGalCer) have been reported to act as receptors of human immunodeficiency virus (HIV) on CD4- cell lines. We show here that these glycolipids are present on CD4+ cells purified from human blood and on in vitro-differentiated monocyte-derived macrophages (MDMs). We investigated the role they could play in HIV infection. Glycolipids of MDMs were characterized at the molecular level by immunolabeling and thin-layer chromatography immune overlay, using a panel of human-, rabbit-, or murine-specific antibodies. GalCer and SGalCer were expressed at the surface of MDMs as assessed by indirect immunofluorescence and flow cytometry analysis, and they could be characterized with specific antibodies in the cellular glycolipid extracts in addition to GM1, GM3, and GD1b gangliosides. Recombinant 125-I-labeled gp160 specifically bound to GalCer, SGalCer, GM1, and GM3 as well as to phospholipids (phosphatidylethanolamine and phosphatidylserine) from MDM extracts. Anti-SGalCer monoclonal antibodies (MAbs), but not anti-GalCer antibodies, entailed limited (30-40%) but significant inhibition of gp160 binding to MDMs. However, the four human anti-SGalCer MAbs and the three murine or rabbit ant-GalCer antibodies tested did not inhibit HIV infection of MDMs, in contrast to CD4 antibody anti-Leu3a tested in parallel. These findings suggests that although HIV envelope glycoprotein can bind to SGalCer and GalCer from CD4+ MDM extracts, these glycolipids do not apparently act as HIV coreceptors nor are they involved in HIV infection of these cells.

Animals↗

PubMed1996

Sensitization of Lewis rats with sulfoglucuronosyl paragloboside: electrophysiological and immunological studies of an animal model of peripheral neuropathy.

Antibodies against sulfoglucuronosyl glycosphingolipids (SGGLs) are known to be present in sera of patients with chronic polyneuropathy associated with IgM paraproteinemia. We recently studied rats sensitized with sulfoglucuronosyl paragloboside (SGPG), a major SGGL species, emulsified with keyhold limpet hemocyanin and Freund's adjuvant. The titer of the IgM class antibodies against SGPG increased up to 1:1,600, while that of the IgG class increased up to 1:800 2 weeks after sensitization. The antibodies showed a high degree of antigenic specificity; no cross-reactivity with other brain glycolipids could be detected. They, however, reacted with human myelin-associated glycoprotein (MAG) by Western blot analysis, but not with rat MAG. These animal models showed minor but clear clinical signs of neuropathy, consisting of mild tail muscle tone loss and walking disabilities. Electrophysiological examination of the sciatic nerves revealed nerve conduction abnormalities which consisted of conduction block and mild decrease in conduction velocity. Thus, our results support the concept that anti-SGPG antibodies may play an important pathogenetic role in this type of chronic neuropathy.

Action Potentials↗

PubMed1996

Myelin-induced experimental allergic encephalomyelitis in Lewis rats: tumor necrosis factor alpha levels in serum and cerebrospinal fluid immunohistochemical expression in glial cells and macrophages of optic nerve and spinal cord.

Tumor necrosis factor alpha (TNFalpha) activity was measured in serum and cerebrospinal fluid (CSF) of Lewis rats after experimental allergic encephalomyelitis (EAE) induction and during the clinical course of acute disease. TNFalpha bioactivity expression preceded the clinical symptoms and paralleled the severity of disease. We further investigated the identity of the central nervous system (CNS) cells involved in TNFalpha expression and their regional localization during EAE. Tissue sections of brain, cerebellum, dorsal spinal cord and optic nerve were studied by indirect double labelling immunofluorescence. Spinal cord white matter and optic nerve showed a widespread TNFalpha immunoreactivity at critical stages of EAE in macrophages/microglia and astrocytes. We have shown changes in CSF/serum albumin ratio and immunoglobulin G index during EAE. Our results confirm the very important role of TNFalpha in EAE.

Animals↗

PubMed1996

[Anti-GM1 gangliosides antibodies in multifocal motor neuropathies].

In a study on 67 chronic neuropathies, we have shown that anti-GM1 antibodies are particularly frequent in multifocal motor neuropathies (MMN) with conduction blocks (17/24 cases). The detection of these antibodies by ELISA necessitates a confirmation by immunodetection on thin-layer chromatography, so as to distinguish the anti-GM1 antibodies present in MMN from natural antibodies which are polyreactive and of low affinity. There is no direct correlation between the anti-GM1 antibody titer, the immunosuppressive treatment and the clinical evolution. Nevertheless, the detection of high titer of anti-GM1 antibodies is an additional argument in favor of treatment by IVIg.

Autoantibodies↗

PubMed1995

Anti-sulfoglucuronyl paragloboside IgM antibodies in amyotrophic lateral sclerosis.

We report here our results on IgM anti-sulfated glucuronyl paragloboside (SGPG) antibodies in sera from patients with amyotrophic lateral sclerosis (ALS). Studies by enzyme linked immunosorbent assay on 72 ALS sera showed IgM polyclonal reactivity towards SGPG in 25 cases. The titer was high in 16 cases. Thin-layer chromatography immuno-overlay showed that reactivity with SGPG was associated to reactivity towards GM1 in five cases and to GM1 and GD1b in one case. Anti-SGPG reactivity was not found in controls and in multifocal motor neuropathy with conduction blocks, in contrast to anti-GM1 antibodies. The presence of anti-SGPG antibodies in ALS patients sera raise again the question of autoimmunity in this pathology.

Amyotrophic Lateral Sclerosis↗

PubMed1995

Exclusion of the candidate locus FSP1 in six families with late-onset autosomal dominant spastic paraplegia.

Hereditary spastic paraplegias are neurological hereditary conditions of unknown aetiology. In pure spastic paraplegia, most of the pedigrees display an autosomal dominant mode of inheritance. A gene for pure autosomal dominant spastic paraplegia (ADSP), termed FSP1, was mapped to chromosome 14q in a large pedigree with early-onset disease. This locus was tested by linkage analysis in six large French kindreds of ADSP with late-onset disease, using four microsatellites spanning a 9 cM interval including FSP1. FSP1 could be excluded in five of the six families, while no evidence for linkage was found in the remaining family. These results suggest that FSP1 is not involved in late onset ADSP, at least in the six families studied.

Adolescent↗

PubMed1995

Multifocal motor neuropathy with conduction block: a study of 24 patients.

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.

Adult↗

PubMed1994

Contribution of transplantations to the understanding of the role of the PLP gene.

We present an overview of the results obtained in a cross-transplantation system using respectively controls, jimpy (jp), and shiverer mutant mice as donors and recipients. Homochronic transplantations (O days into O days) demonstrated that jp environment is non-toxic for non-jp cells and that, contrary to in vitro, jp oligodendrocytes phenotype cannot be modified by environmental factors at this age. Transplantations of embryonic fragments into the newborn brain demonstrated that in contrast to oligodendrocyte precursors contained in fragments of newborn tissue, jimpy embryonic stem cells are sensitive to environmental factors able to modulate the proportion of surviving oligodendrocytes. In addition, these series evidenced a disjunction between the surviving and the myelinating capacity of jp cells demonstrating a pleiotropic effect of the jp mutation on oligodendrocyte biology. Results are discussed with regards to the recent molecular biological finding on the role of the DM20/PLP gene.

Animals↗

PubMed1994

Human immunoglobulin treatment of multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy.

Intravenous human immune globulin (IVIg) has been proposed for the treatment of various peripheral neuropathies that are considered to be immunemediated. The results are reported of an open trial conducted in multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy. Six cases with multifocal motor neuropathy, selected on clinical and electrophysiological criteria (four of six patients also had significantly high anti-GM1 titres), received IVIg monthly, at doses varying from 1.6 to 2.5 mg/kg, over three to 13 months. The initial response to treatment was dramatic in 3/6 cases (with improvement of at least two grades on the MRC scale in the five more severely affected muscles). The final evaluation showed a good result in 4/6 cases, but the conduction blocks were not significantly reduced. In 13 other cases with polyneuropathy associated with IgM monoclonal gammopathy of unknown significance, IVIg was of benefit, with improvement of at least one grade on the Prineas score, in 4/7 cases previously treated with immunosuppression and 2/3 cases not treated before IVIg. In the last group of four patients with polyneuropathy and IgG monoclonal gammopathy, IVIg was followed by clinical improvement in the two cases with a chronic demyelinating polyneuropathy.

Humans↗

PubMed1993

Reactivity of a human monoclonal anti-GM1 and anti-GD1b IgM antibody with human neurons in cultures.

A serum containing a monoclonal IgM lambda with anti-GM1 and anti-GD1b activity was obtained from a patient with upper motor neuron syndrome. By indirect immunocytochemical techniques with double staining, the patient's IgM strongly stained membranes of neurons in primary cultures of fetal central and peripheral nervous system. It was cytotoxic for neurons in two human neuroblastoma established cell lines in a complement-dependent chromium release assay. These results are in keeping with the hypothesis of a direct pathogenetic role of such monoclonal anti-GM1 and GD1b IgM antibodies.

Antibodies, Monoclonal↗

PubMed1993

Cerebellar soluble lectin and its glycoprotein ligands in the developing brain of control and dysmyelinating mutant mice.

The levels of an endogenous lectin, the cerebellar soluble lectin (CSL) and of its endogenous glycoprotein ligands were studied using immunoblotting and affinoblotting techniques in the forebrain of quaking, shiverer and jimpy dysmyelinating mutant mice and their respective control littermates during the postnatal development. In the controls of the mutant mice, the level of CSL showed an important increase between days 5-18 then a stabilization, although at all ages the level of CSL was reduced (at least 15%) in the control littermate of the shiverer mutant. In the shiverer mutant the developmental pattern is similar to the control but was reduced by 50% as compared to the control. In the jimpy mutant an erratic development of CSL was observed which was with quasi absence of CSL at days 12 and 25. Variation of CSL levels in the quaking brain were also observed. CSL glycoprotein ligands also showed variable developmental profiles with a special persistence with ageing of CSL-binding glycoproteins in the quaking and jimpy mice. Developmental variations were also observed between the different control littermates. These results are discussed in view of developmental roles attributed to CSL and its glycoproteins ligands in cell adhesion mechanism during brain ontogenesis and especially myelination.

Aging↗

PubMed1993

Adrenoleukodystrophy in France: an epidemiological study.

An epidemiological study was conducted in France to estimate the prevalence of adrenoleukodystrophy, a severe neurologic X-linked disorder affecting boys and young men. 129 cases were collected. Analysis of all cases born between 1956 and 1986 with available clinical history allowed the calculation of the lowest estimation of the prevalence: 1 in 100,000 male births.

Adolescent↗

PubMed1993

[Symptomatic heterozygotic adrenoleukodystrophy in adults. 10 cases].

Adult adrenoleukodystrophy is a X-linked peroxisomal disease associated with the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids. The diagnosis is established on the demonstration of elevated VLCFA in blood and cultured skin fibroblasts. Women are affected in nearly 15% of cases and neurological symptoms and/or signs develop in 53% of them. Identifying these women is important because of genetic counseling and a possible therapeutic approach. Ten cases of symptomatic heterozygous adult adrenoleukodystrophy are reported. Mean age at the time of diagnosis was 44.6 +/- 9.3 years. All patients presented with spastic paraparesis with inconstant and mild sensory or bladder disturbances. Cognitive impairment was present in 1 case. Cerebrospinal fluid was normal. Adrenal function in response to tetracosactide injection was abnormal in 1/7 cases. Electromyography detected a peripheral neuropathy in 1 case. Somatosensory evoked responses were abnormal in all cases, visual and auditory evoked responses in respectively 3/6 cases and 3/4 cases. Brain MRI detected non specific abnormalities in 3/7 cases; spinal cord MRI was normal in 3/3 cases. The familial history was helpful for the diagnosis in 3/10 cases. Examination of pedigrees detected 5 hemizygous and 1 asymptomatic heterozygous cases. All the patients were enrolled in a dietary study which adret with low VLCFA is currently under evaluation.

Adrenoleukodystrophy↗

PubMed1993

High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy.

We identified a patient suffering from late-infantile metachromatic leukodystrophy (MLD) who has a residual arylsulfatase A (ARSA) activity of about 10%. Fibroblasts of the patient show significant sulfatide degradation activity exceeding that of adult MLD patients. Analysis of the ARSA gene in this patient revealed heterozygosity for two new mutant alleles: in one allele, deletion of C 447 in exon 2 leads to a frameshift and to a premature stop codon at amino acid position 105; in the second allele, a G-->A transition in exon 5 causes a Gly309-->Ser substitution. Transient expression of the mutant Ser309-ARSA resulted in only 13% enzyme activity of that observed in cells expressing normal ARSA. The mutant ARSA is correctly targeted to the lysosomes but is unstable. These findings are in contrast to previous results showing that the late-infantile type of MLD is always associated with the complete absence of ARSA activity. The expression of the mutant ARSA protein may be influenced by particular features of oligodendrocytes, such that the level of mutant enzyme is lower in these cells than in others.

Alleles↗

PubMed1993

[Treatment of immune deficient neuropathies with intravenous polyvalent immunoglobulins. An open study of 16 cases].

UNLABELLED: Between June 1989 and February 1992, in an open controlled study 16 patients with various types of polyneuropathy were treated with high-dose intravenous immunoglobulins (IgIV). Every month during 3 months, each patient received three courses of IgIV in doses of 0.4 g/kg/day during 5 successive days. The trial was discontinued in case of no response or if the neuropathy was considered as being in remission. In the other cases, at most one course of IgIV was given once a month if there was significant improvement (assessed by previously published clinical functional scales, electrophysiological examinations and titers of specific antibodies), or spaced at intervals which varied according to each patient, and sometimes in low doses. RESULTS: 1) A first group of 6 patients had chronic demyelinating polyneuropathy with severe motor disability. The first infusions of IgIV resulted, in 4/6 cases, in a dramatic improvement which lasted under regularly spaced courses in lower doses. 2) Four patients had chronic neuropathy associated with monoclonal IgM gammopathy of undetermined significance (3 had anti-MAG and anti-SPG antibodies, and 1 had anti-GD1a and GD1b antibodies) and had not been improved by the usual immunosuppressive treatments. In 1 case the IgIV treatment had to be discontinued because of skin allergy. In the remaining 3 patients the clinical disorders (mainly the sensory ones) were reduced, but no significant improvement of neurophysiological or immunological data was observed. 3) Three patients had a purely multifocal motor neuropathy with persistent conduction blocks at EMG and high titers of anti-GM1 antibodies in 2/3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Glial biology and disorders.

Much work has been devoted this year to the localization and mode of expression of growth factors and cytokines. Although it is not possible to extrapolate directly from in vitro to in vivo conditions, the plasticity of glial cells seems to be very influenced by growth factors. Astrocytes in vivo do not express many growth factors during normal conditions, but a pathologic event can lift these restrictions. Cytokines and their receptors have been localized on neuronal or glial cell types. The programmed cell death, well identified in neurons, seems to occur also in oligodendrocytes and may be influenced by survival factors. In the adult brain, glial progenitors are present and may be a potential source to generate myelinating oligodendrocytes for myelin repair. In the peripheral nervous system, axonal-Schwann cell signaling may function in both directions during development. Some animal neurologic mutants are models for human diseases; one of them, the Trembler mouse, has effectively led to the genetic characterization of Charcot-Marie-Tooth disease type 1a. As for myelin destruction, the relationship between demyelination and inflammation is still not very clear.

Cell Death↗