Search PubMed⌕ Search

Biomedical subjects

J C Vernant

Publications and source records attributed to J C Vernant.

At least 37 records · Page 2Linked to original sources

A search for human T-cell leukemia virus type I in the lesions of patients with tropical spastic paraparesis and polymyositis.

We searched for the presence of human T-cell leukemia virus type I (HTLV-I) sequences in central nervous system and muscle lesions of 3 patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and 3 patients with HTLV-I-associated polymyositis. Proviral DNA coding for the Tax protein was found by polymerase chain reaction amplification in DNA extracted from lesions of every patient with TSP/HAM or HTLV-I-associated polymyositis. In contrast, viral RNA was found occasionally by in situ hybridization in muscle lesions of some patients with polymyositis, but was never found in central nervous system lesions of TSP/HAM patients.

DNA, Viral↗

IgG autoantibody response in HTLV-I-infected patients.

Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestation including adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases, however, infected patients remain asymptomatic. The participation of the immune system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG antibody response of HTLV-I-infected individuals has been investigated using both ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be recognized by antibodies from patients with various systemic autoimmune diseases, and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The results were compared with the reactivity of sera from individuals with non-HTLV-I-related neurological diseases and healthy blood donors. Raised levels of autoantibodies reacting with several nuclear and cytoplasmic antigens were found in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals, both the prevalence and level of IgG antibodies were lower and directed only against a restricted set of antigens. The mechanism of induction of these antibodies still remains obscure. However, the results show that a significant autoimmune response exists in these patients and it may contribute to the pathogenesis of the disease.

Adult↗

Clinical characteristics of HTLV-1 associated dermato-polymyositis. Seven cases from Martinique.

Myositis linked to HTLV-1 is unfrequent. Over a period of 8 years, 14 patients with inflammatory myopathy were diagnosed in Martinique. Seven were seropositive for HTLV 1 antibody; the clinical and pathological data of whom are presented herein. Five patients presented with polymyositis, two with dermatomyositis. All seven patients had extra-muscular clinical features including neuropathy (4/7) and myelopathy (6/7), resulting in a quite peculiar clinical picture. Muscle biopsy showed a neurogenic process combined with myositic changes in 3/7 patients. Corticotherapy led to dramatic improvement in only one case, but with no sustained effect. HTLV 1 may be considered the etiological agent of this form of dermato-polymyositis, characterized by a clearly distinctive clinico-pathological picture, and a poor response to corticotherapy. As in the case of tropical spastic paraparesis/HTLV 1 associated myelopathy, careful assessment of non-steroidal therapy is now warranted.

Adult↗

[Loss of psychic auto-activation. Obsessive-compulsive behavior. Toxoplasmic abscess of the basal ganglia].

A 34 year old woman with AIDS presented with adynamia and obsessive-compulsive behaviour. CT scan revealed bilateral toxoplasmic lesions involving basal ganglia. The neuropsychological picture resolved under specific antitoxoplasmic treatment. However, relapse of toxoplasmosis occurred in associating with the same behavioral changes. This is the first case of such a syndrome due to infectious lesions, and in which improvement through transient, was observed.

AIDS-Related Opportunistic Infections↗

Autosomal dominant cerebellar ataxia type I linked to chromosome 12q (SCA2: spinocerebellar ataxia type 2).

Spinocerebellar ataxia 2 (SCA2) is one of the loci for the clinically and genetically heterogeneous group of autosomal dominant type I cerebellar ataxias. After initial linkage to chromosome 12q in Cuban families, SCA2 was shown to be the gene responsible for the disease in Italian, Tunisian, French-Canadian, Austrian-Canadian and Martinican kindreds with dominant ataxia, and the candidate interval was reduced to 6.4 cM between markers D12S84 and D12S79. Comparison of patients from families of different geographical origins clearly demonstrates the clinical interfamilial variability of the clinical signs which reaches statistical significance for the frequency of extrapyramidal rigidity, postural tremor and dementia. The most striking difference between the 29 Martinican SCA2 patients and those with SCA1 on chromosome 6p or SCA3/MJD on chromosome 14q is the greater frequency of hyporeflexia in the former. A mean 12.5 year anticipation is observed, with a more rapid clinical course of the disease in successive generations, indicating that an expanded trinucleotide repeat probably constitutes the underlying molecular mechanism.

Adolescent↗

[Involvements of the peripheral nervous system and skeletal muscles in HTLV1-related paraplegia. Study of 70 cases seen in Martinique].

The main neurological manifestation due to Human T-Cell Lymphotropic Virus type (HTLV1) infection is a chronic spastic paraparesis called HTLV1-associated paraparesis (HAP). Since 1985, we observed in Martinique (French West Indies) 276 cases of HAP. Among them, 70 patients fulfilled clinical, electrophysiological or histological criteria of associated peripheral nervous system involvement (42/70), myositis (8/70), or both (20/70). Muscle biopsy revealed neurogenic atrophy of muscle fibers or myositic changes in 41/70. Neuromuscular involvement was only mild in 19/70. On the other hand, 25 patients presented with a syndrome mimicking amyotrophic lateral sclerosis, and 7 other patients with features of polymyositis. This study shows that neurological manifestations associated to HTLV1 infection may be more complex than the well-known chronic spastic paraparesis, since 25.4% of the HAP Martinican patients exhibit neuropathic or myositic features.

Electromyography↗

[Vasculitis and neurologic manifestations related to HTLV-1].

OBJECTIVES: The most common neurological picture associated with HTLV-1 infection is a slowly progressive spastic paraplegia often involving nerve and muscle inflammation. We report here six cases of inflammatory vasculitis of the nervous system observed among HTLV-1 infected patients. METHODS: HTLV-1 infection was diagnosed in 6 female patients, mean age 58 years (range 40-77 years) using ELISA, Western blot or polymerase chain reaction. RESULTS: All 6 patients presented a pyramidal syndrome which was associated with peripheral neuropathy in 3, myositis in 1 and a sicca syndrome in 3. Two groups of patients could be identified. In 3 patients, the neurological picture was typical of HTLV infection; pathology examination of biopsy material revealed necrozing vasculitis. In 3 other patients, the clinical course was particularly rapid, highly suggestive of anterior spinal artery infarction, associated, in 2, with a major inflammatory syndrome. CONCLUSION: These 6 cases demonstrate that vasculitis can be associated with HTLV-1 infection as has been observed in HIV-infected patients. In certain cases, clinical signs of vasculitis may be lacking while in others they may dominate the clinical manifestations.

Adult↗

IL-2-dependent HTLV-I-infected T cells escape from non-specific, MHC-unrestricted cellular cytotoxicity.

The susceptibility of NK cell-mediated cytolysis was compared between 5 human HTLV-I-transformed T cell lines and 10 newly established IL-2-dependent HTLV-I-infected lines. None of the cell lines were killed after 4 hr incubation with normal PBMC. However, after 20 hr, 3 HTLV-I-transformed lines were significantly lysed. All the HTLV-I-infected lines, except 2, weakly inhibited the NK cell-mediated lysis of K562 targets. They showed a reduced ability to bind normal PBMC as compared with control NK-sensitive T cell lines. The IL-2-dependent lines remained unaffected by PBMC from HTLV-I-infected individuals, including the autologous donors. In contrast to the HTLV-I-transformed lines, they were weakly lysed or not lysed at all by LAK cells and only 5 were killed by ADCC with HTLV-I+ sera and normal PBMC. Taken together, the results show that IL-2-dependent HTLV-I-infected T cells strongly resist NK cell-mediated cytolysis at a post-binding level and suggest that such cells may escape in vivo from non-specific, MHC-unrestricted cellular cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗

Identification of novel neutralization-inducing regions of the human T cell lymphotropic virus type I envelope glycoproteins with human HTLV-I-seropositive sera.

The humoral immune response in sera from 30 human T cell lymphotropic virus type I (HTLV-I)-positive individuals from Martinique in the French West Indies was studied. The subjects were subdivided into those suffering from TSP/HAM and those being asymptomatic. In general, TSP/HAM patient sera seemed to contain more virus-specific antibodies than did the sera from the asymptomatic subjects. Three of the 13 TSP/HAM sera and 1 of the 17 asymptomatic sera contained HTLV-I-specific IgM antibodies, whereas 6 and 5 sera, respectively, contained IgA antibodies. By correlating the ability of patient sera to inhibit HTLV-I-induced syncytia with their antibody reactivity in ELISA to 42 synthetic peptides, together corresponding to the entire envelope glycoprotein of HTLV-I, a number of putative neutralizing domains were identified. Eight synthetic peptides representing the regions with the highest coefficient of correlation between neutralizing titer and ELISA reactivity were employed to specifically adsorb potentially neutralizing antibodies, and were also used directly, without sera, in the syncytium-neutralizing test. By those techniques, three novel and two previously described domains that seemed to contain neutralizing epitopes were identified. Two of the novel neutralizing sites resided in the external glycoprotein (gp46) and were contained within amino acids 53-75 and 287-311, respectively, and one was located in the transmembrane glycoprotein (gp21) within amino acids 346-368. Our findings may have implications for the rational design of subunit vaccines for prevention of and/or alteration of the clinical outcome of HTLV-I-related diseases.

Adult↗

[Ophthalmologic manifestations in spinal cord diseases caused by HTLV-I virus. Clinical study of 30 cases].

We present the results of ophthalmologic examinations of a consecutive series of 30 patients with HTLV-I associated myelopathy. This is the first ophthalmologic prospective study reported outside the Japanese endemic area. Twenty-one of the patients (70%) had kerato-conjunctivitis sicca in addition to accessory salivary gland lymphocytary infiltration in 7. Two cases of uveo-papillitis, 1 case of cotton-wool spots and 3 cases of retinochoroidal degeneration were also observed. Moreover, an aliquot of the aqueous humour was collected from the anterior chamber in 5 patients and showed high titer of HTLV-I antibodies for the 2 patients with uveo-papillitis. We propose different hypotheses to explain the physiopathologic characteristics of these features.

Adult↗

[Uveo-papillitis associated with paraparesis caused by HTLV-1 virus].

The human T-lymphotropic retrovirus type I (HTLV-1), isolated in 1980, has been shown to be responsible for two distinct systemic diseases: adult T-cell leukemia and HTLV associated myelopathy (HAM). Recently, an ever increasing number of publications have described other disorders associated with HAM. We report a case of uveitis-optic disc neuritis which, to our knowledge, had not been previously described. The fact that both uvea and optic disc were inflamed would suggest that immune-mediated reactions are involved in the pathogenesis of HAM.

Adult↗

Expression of HTLV-I Env and Tax recombinant peptides in yeast: identification of immunogenic domains.

A peptide library of HTLV-I Env and Tax proteins was constructed in yeast in order to characterize which domains of these proteins are immunogenic in HTLV-I-infected individuals. Five yeast colonies (A to E) were selected using HTLV-I positive plasma, and one yeast colony (F) was selected using rabbit anti-Tax sera. Plasmid DNA present in each positive clone was recovered and sequenced. Overlapping clones A to E covered the C-terminal part of the gp46 exterior glycoprotein (aa 197 to 305) and were all glycosylated. Clone F encoded the C-terminal 25 aa of Tax (aa 329-353). Recombinant peptides were recognized by more than 40% of the HTLV-I positive human sera, confirming that they are major immunodominant domains. We studied the antibody response to each recombinant peptide in patients with TSP/HAM and asymptomatic carriers. Higher absorbance values were obtained with sera from TSP/HAM patients than from asymptomatic carriers, but the difference between the two groups was not statistically significant. Our study confirms that the COOH-terminal region of gp46 is highly immunogenic in HTLV-I-infected individuals and demonstrates a new immunogenic epitope of the Tax protein.

Amino Acid Sequence↗

[Multiple sclerosis in the black population].

Numerous epidemiological studies showed that The occurrence of multiple sclerosis (MS) was the result of genetic factors varying by ethnic group as well as geographical and environmental factors. It is difficult to estimate exactly the prevalence of MS among black Africans. Nevertheless it's possible to state that the disease is rare but present among those populations. Among black Americans prevalence of MS seems related to the degree of mixture with white population. Among West Indians the occurrence of MS is closely related to an environmental factor acquired in Europe before 15 years of age. Those data confirm the existence during childhood and adolescence of a critical period during which an environmental factor is acquired in regions of high prevalence for MS.

Adolescent↗

[Paraplegia associated with HTLV 1 in Martinique. Study of 271 cases including 70 with neuromuscular involvement].

To date, 271 cases of HTLV1-associated paraplegia have been observed in Martinique (French West Indies). The clinical picture consisted mostly in a spastic paraparesis or paraplegia with sphincter disturbances (80%) and lower limbs pains (60%). The severity of the disease appeared variable: after a mean disease duration of 6.5 years, 40% of the patients could walk without help, 35% used a single crutch, and 25% used a couple of crutches or were confined to a wheelchair. A variable neuromuscular component was observed in 70 cases (25.4%). In 38 cases, the peripheral signs (SIGNS) or the myositis were only mild. In contrast, 25 patients presented with severe amyotrophy evoking amyotrophic lateral sclerosis, and 7 other had features of dermatopolymyositis. Lastly, an extra-neural spreading of the disease was extremely frequent, including lymphocytic alveolitis (76%), sicca syndrome (69%) and more rarely uveitis, arthritis or vasculitis.

Adolescent↗

[Symptomatic spinal intra-dural arachnoid cyst. Apropos of a case with magnetic resonance imaging].

The authors report a case of intradural posterolateral spinal arachnoid cyst diagnosed by Magnetic Resonance Imaging (MRI) in a 59-year-old woman. Ten years before, she started to suffer from burning sensation of the left lower limb aggravated by head movements. Physical examination was normal except a sensory dissociation below T10. A myelography was considered as normal. Three years later, motor disturbances occur with progressive weakness. Examination showed asymmetrical spastic paraparesis with a right predominance. On MRI, the spinal cord was displaced at T6-T7 level by a posterior intradural mass with a similar signal than CSF; furthermore, at this level, there was an intramedullary hyposignal on T1 weighted sections. The diagnosis of spinal intradural arachnoid cyst was confirmed at surgery. Microscopic examination of the cyst wall showed fibrous tissue with mild lymphocytic infiltration. Rapid recovery of legs weakness followed, but abnormalities of spinothalamic functions persisted. The clinical characteristics and the MRI data are discussed. The authors conclude that this arachnoid cyst had an inflammatory origin.

Arachnoid Cysts↗