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C Tranchant

Publications and source records attributed to C Tranchant.

At least 37 records · Page 2Linked to original sources
PubMed2004

Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci.

Autoantibodies against the muscle acetylcholine receptor (AChR) play an essential role in the pathophysiology of autoimmune myasthenia gravis (MG). Their serum titers, however, vary considerably among patients. Our aim was to investigate whether their variation might be explained by genetic factors. Using different methods, we have obtained strong evidence for a three-locus association influencing autoantibody titers in MG patients with thymus hyperplasia or with a normal thymus. Two of the loci, one encoding the AChR alpha-subunit, the other encoding the alpha-chain of the class II antigen-presentation molecule, HLA-DQ, demonstrated interaction to determine high autoantibody titers. The third locus was associated with the 8.1 ancestral HLA haplotype. It exerted an additive effect and it is postulated to have a nonantigen specific immunoregulatory function. Our study demonstrates for the first time that polymorphism of an autoantigen gene may quantitatively modify the immune response against it. Altogether, the data lend support to a three-gene model to explain autoantibody expression in a subset of MG patients.

Autoantibodies↗
PubMed2003

Phenotypic variability of aprataxin gene mutations.

The clinical and genetic features of three non-Portuguese and non-Japanese patients with aprataxin gene mutations are reported. Patient 1 came from Italy and presented with typical ataxia with ocular motor apraxia (OMA). She was homozygous for the W279X nonsense mutation, which is associated with the Portuguese founding haplotype. Patients 2 and 3 were French siblings and did not present with either OMA or hypoalbuminemia. They were compound heterozygous for the nonsense W279X mutation and a missense K197Q mutation.

Adult↗
PubMed2003

[Lyme borreliosis].

Lyme disease is a multisystemic disease caused by a spirochete, Borrelia Burgdorferi that is transmitted by ticks. A clinical diagnosis is easy when a tick bite is followed 3 weeks later by erythema migrans, than by involvement of nervous system, joints or heart. In case of neuroborreliosis, serological tests, performed in blood and cerebro-spinal fluid, support the diagnosis and patients recover rapidly with antibacterial treatments. However an accurate diagnosis remains sometimes problematic, especially distinction between a coincidental positive serologic test and a nervous system Lyme borreliosis which require antibiotics. Furthermore, the role of autoimmunity in the pathophysiology of late Lyme disease, antibiotic choice in early disease, duration of treatment, and utility of vaccination are discussed.

Animals↗
PubMed2002

[Prion diseases].

Creutzfeldt-Jakob disease, kuru, Gerstmann Sträussler Scheinker syndrome and fatal familial insomnia in humans, as well as scrapie and bovine spongiform encephalopathy, in animals, are fatal disorders of the central nervous system that are part of the group of transmissible spongiform encephalopathies, (TSE) or prion diseases. Neuronal intracellular spongiosis and the accumulation of abnormal, protease resistant prion protein in the nervous central system characterize TSE. The conformational change of a host protein, prion protein, into a pathological isoform is the key pathogenetic event in TSE. Despite their relative rarity, prion diseases have a great impact on the scientific community and society in general. There are two major reasons: first, the heretical hypothesis of a disease transmitted by an "infectious protein" in the absence of nucleic acid, the basis of the conformational transmissibility concept; second, the panic originated from the appearance of new variant Creutzfeldt-Jakob disease and the evidence linking it to the exposure of humans to bovine spongiform encephalopathy via food contaminated by affected bovine tissue. Novel therapeutic approaches are examined.

Brain↗
PubMed2001

Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies.

BACKGROUND: MG is an autoimmune disease of the neuromuscular junction. MG with thymus hyperplasia has been associated with, but not genetically linked to, the HLA-DR3 haplotype. OBJECTIVE: To re-evaluate the association of HLA with MG in 656 patients with generalized disease and to test linkage of HLA to MG with thymus hyperplasia. METHOD: Patients were genotyped for HLA-DRB1. Data analysis included case-control comparisons after subgrouping patients by thymus histopathology. The transmission of parental alleles to MG offspring with thymus hyperplasia was studied in simplex families using the transmission/disequilibrium test (TDT) as a test of linkage. RESULTS: MG with thymus hyperplasia was positively associated with DR3 (OR = 4.5, p = 1 x 10(-6)) and negatively associated with DR7 (OR = 0.28, p = 1 x 10(-6)), based on both case-control comparisons and TDT. No association was detected with thymomas. Conversely, patients who lacked thymus anomalies but expressed anti-titin antibodies (ATA) had an increase of DR7 (OR = 2.08, p = 4 x 10(-3)) and a decrease of DR3 (OR = 0.33, p = 9 x 10(-3)). CONCLUSIONS: The authors established linkage of HLA to MG and thymus hyperplasia, defining the MYAS1 locus. Moreover, DR3 and DR7, or closely linked genes, have opposing effects on MG phenotypes. Nonthymomatous patients with ATA may be a pathogenetically distinct subset of MG patients.

Adult↗
PubMed2001

Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients.

BACKGROUND: Titin is the major autoantigen recognized by anti-striated muscle antibodies, which are characteristic of generalized myasthenia gravis (MG). OBJECTIVE: To seek a correlation between anti-titin antibodies and other features of MG patients, including histopathology, age at diagnosis, anti-acetylcholine receptor (anti-AChR), autoantibody titers, and clinical severity. METHODS: A novel, highly specific radioligand assay was performed on a large group of 398 patients with generalized MG. RESULTS: Among thymectomized patients, anti-titin antibodies were present in most patients with thymoma (56/70 [80%]), contrasting with only a minority of patients with thymus atrophy or hyperplasia (17/165 [10%]). They were also present in 64 (41%) of 155 nonthymectomized patients who had a radiologically normal thymus. In these patients and in those who had a histologically normal thymus, anti-titin antibodies were associated with a later age at onset of disease and with intermediate titers of anti-AChR antibodies. After controlling for these 2 variables, disease severity was not significantly influenced by anti-titin antibodies. CONCLUSIONS: Anti-titin antibodies are a sensitive marker of thymoma associated with MG in patients 60 years and younger, justifying the insistent search for a thymoma in MG patients of this age group who have these antibodies. In nonthymoma patients, anti-titin antibodies represent an interesting marker complementary to the anti-AChR antibody titer, identifying a restricted subset of patients. These clinical correlations should prompt further studies to examine the mechanisms leading to the production of anti-titin antibodies.

Adult↗
PubMed2001

Prospective clinical study of writer's cramp.

Sixty-five consecutive patients with writer's cramp were studied prospectively to evaluate clinical and demographic features, the number of writing hours per day at dystonia onset, and the existence of trigger events. Assessment of writing and drawing was done on a standardized test using categorical scales. The importance of subjective handicap and pain, of postural and action tremor, the abnormal features of hand grip and the occurrence of mirror dystonia (dystonia occurring in the dominant hand when writing with the other hand) were studied. Thirty-two patients had simple writer's cramp, whereas the others had complex writer's cramp with several activities other than writing involved. No significant differences were seen in age of onset, legibility, pain, and handicap in these two groups. Seven patients had a family history of focal dystonia and six of them had a complex form of writer's cramp. Mirror dystonia was seen in 29 patients and in some it appeared useful to distinguish dystonic movements from secondary compensatory strategies.

Adult↗
PubMed2001

Disease expression of Lyme borreliosis in northeastern France.

Since very little is known about the clinical expression of Lyme borreliosis in Western Europe, a 3-year prospective study was conducted that included all patients seen for suspected Lyme borreliosis at the Strasbourg University Hospital in northeastern France. The diagnosis of Lyme borreliosis was made on the basis of the presence of erythema migrans or on the basis of another suggestive clinical manifestation and laboratory confirmation. A total of 132 patients, 70 women and 62 men, mean age 54 years, had Lyme borreliosis according to these criteria. Within this study group, 77% of the patients were regularly exposed to tick bites and 64% could remember one. Erythema migrans, the most frequent clinical manifestation, occurred in 60% of the patients and was the only sign of Lyme borreliosis in 40%. Lymphocytoma and acrodermatitis chronica atrophicans were rare (1 and 3 patients, respectively). Nervous system involvement (mainly radiculoneuropathy), the second most common clinical manifestation, was found in 40% of the patients and was the only sign of Lyme borreliosis in 22%. Musculoskeletal involvement was present in 26% of the patients and was an isolated finding in 14%. During the study period, no patient was diagnosed with Lyme carditis. There was serological evidence of Lyme borreliosis in 75% of the cases and direct evidence of borrelial infection in 10 (7.5%). The results show that the clinical expression of Lyme borreliosis in northeastern France is similar to that in other European countries but different from that in North America.

Adolescent↗
PubMed2001

[Hemicontracture and facial myokimia as the first manifestation of multiple sclerosis].

Continuous facial myokimia (CFM) are characterized by a contracted facial appearance and vermicular movements that spread across a hemiface. Pontine lesions are their most frequent cause. Although their occurrence during the course of multiple sclerosis is not uncommun, CFM are rarely the first sign of the disease. We report two cases of CMF as first manifestation of multiple sclerosis. Multiple sclerosis is the first diagnosis to suspect in young people with CFM.

Adult↗
PubMed2000

A 7-kDa prion protein (PrP) fragment, an integral component of the PrP region required for infectivity, is the major amyloid protein in Gerstmann-Sträussler-Scheinker disease A117V.

Gerstmann-Sträussler-Scheinker disease (GSS) is a cerebral amyloidosis associated with mutations in the prion protein (PrP) gene (PRNP). The aim of this study was to characterize amyloid peptides purified from brain tissue of a patient with the A117V mutation who was Met/Val heterozygous at codon 129, Val(129) being in coupling phase with mutant Val117. The major peptide extracted from amyloid fibrils was a approximately 7-kDa PrP fragment. Sequence analysis and mass spectrometry showed that this fragment had ragged N and C termini, starting mainly at Gly88 and Gly90 and ending with Arg148, Glu152, or Asn153. Only Val was present at positions 117 and 129, indicating that the amyloid protein originated from mutant PrP molecules. In addition to the approximately 7-kDa peptides, the amyloid fraction contained N- and C-terminal PrP fragments corresponding to residues 23-41, 191-205, and 217-228. Fibrillogenesis in vitro with synthetic peptides corresponding to PrP fragments extracted from brain tissue showed that peptide PrP-(85-148) readily assembled into amyloid fibrils. Peptide PrP-(191-205) also formed fibrillary structures although with different morphology, whereas peptides PrP-(23-41) and PrP-(217-228) did not. These findings suggest that the processing of mutant PrP isoforms associated with Gerstmann-Sträussler-Scheinker disease may occur extracellularly. It is conceivable that full-length PrP and/or large PrP peptides are deposited in the extracellular compartment, partially degraded by proteases and further digested by tissue endopeptidases, originating a approximately 7-kDa protease-resistant core that is similar in patients with different mutations. Furthermore, the present data suggest that C-terminal fragments of PrP may participate in amyloid formation.

Adult↗
PubMed2000

Pallido-Luysio-Nigral atrophy revealed by rapidly progressive hemidystonia: a clinical, radiologic, functional, and neuropathologic study.

Pallido-luysio-nigral atrophy (PLNA) is a rare neurodegenerative disease in which the clinical and radiologic correlates have not yet been clearly established. A 62-year-old man insidiously developed dystonic postures, choreoathetoid movements, slowness, and stiffness, which initially affected the right hand and foot and progressively spread to the entire right side. T2-weighted magnetic resonance imaging showed increased signal intensity in both left and right medial pallida and in the left substantia nigra. Tests using HMPAO-SPECT and FDG-PET demonstrated left cortical hyperperfusion and hypermetabolism, whereas the left lenticular nucleus was slightly hypometabolic. At age 65, abnormal movements and postures involved all four limbs and the axis causing major gait disturbances, and facial and bulbar muscles atrophied resulting in dysarthria, dysphagia, and impaired breathing. Diffuse amyotrophy and fasciculations also appeared. Death occurred at age 66, 4 years after onset. At autopsy, severe bilateral neuronal loss and gliosis restricted to the pallidum, the subthalamic nucleus, the substantia nigra, and the hypoglossal nucleus were noted, accounting for the diagnosis of PLNA with lower motor neuron involvement. Progressive hemidystonia with adult onset represents an unusual clinical presentation for this disorder. Moreover, this observation indicates that a diagnosis of PLNA should be considered for specific magnetic resonance imaging, SPECT, and/or PET data, and suggests that in PLNA, pallidal dysfunction might play a key role in the dystonic presentation.

Age of Onset↗
PubMed2000

MRI in multiple sclerosis of the spinal cord: evaluation of fast short-tan inversion-recovery and spin-echo sequences.

We compared the sensitivity of T2-weighted spin-echo (FSE) and fast short-tau inversion-recovery (fSTIR) sequences in detection of multiple sclerosis of the spinal cord in 100 consecutive patients with clinically confirmed multiple sclerosis (MS); 86 patients underwent also brain MRI. In all, 310 focal lesions were detected on fSTIR and 212 on T2-weighted FSE, spinal cord lesions were seen better on fSTIR images, with a higher contrast between the lesion and the normal spinal cord. In 24 patients in whom cord plaques were shown with both sequences, the cranial study was normal or inconclusive. Assessment of spinal plaques can be particularly important when MRI of the brain is inconclusive, and in there situations fSTIR can be helpful.

Adult↗
PubMed2000

Is clonidine growth hormone stimulation a good test to differentiate multiple system atrophy from idiopathic Parkinson's disease?

Clonidine, a centrally active alpha 2-adrenoreceptor agonist used to lower blood pressure, has been proposed to differentiate central from peripheral autonomic deficits and multiple system atrophy (MSA) from untreated idiopathic Parkinson's disease (IPD). A lack of growth hormone (GH) increase after clonidine infusion is found in patients with MSA, but not in those with IPD or with pure autonomic failure. We studied 19 IPD and 7 MSA patients to assess whether this test could be used in clinical practice to distinguish MSA from IPD, whatever the stage of the disease. Serum GH levels were measured 15, 30, 45 and 60 min after a 10-min infusion of 2 micrograms/kg clonidine. GH levels remained stable after clonidine infusion in all 7 MSA patients but increased in only 12 of the 19 IPD patients, while remaining stable in the other 7. No correlation was found with the presence of orthostatic hypotension. We conclude that the GH response to clonidine infusion has a very high sensitivity (100% in our series and in previous studies) for the diagnosis of MSA. However, this response cannot be used as a diagnostic test because of its poor specificity.

Aged↗