Two successive hepatitis C virus infections in an intravenous drug user

We report the case of an occasional intravenous drug user who developed two successive hepatitis C virus (HCV) infections. The first infection led to seroconversion (anti-HCV antibodies detected) and the detection of HCV RNA in serum. After a spontaneous recovery (normalization of alanine aminotransferase levels and HCV RNA clearance), a second HCV infection was observed, with the recurrence of HCV viremia. Antibody directed against HCV serotype 1 was detected throughout the follow-up monitoring, but two different HCV strains were identified during the two infectious episodes: genotype 1a for the first and genotype 3a for the second. This observation shows that primary HCV infection does not confer protective immunity against subsequent infection with viruses of other genotypes. This may hamper the development of a vaccine. Conflicting results were obtained in genotyping and serotyping assays, suggesting that the serotyping method cannot be used to identify the HCV type in patients, such as intravenous drug users, who are exposed to successive HCV infections.     

Acrofacial dysostoses

A female baby was born with phocomelia, bilateral cleft lip and palate, marked micrognathia, malar hypoplasia, absence of lower eyelids, and absence of external ears. Radiological examination showed hypoplastic pectoral and pelvic girdles, short humeri and femora, with absence of forearms and legs, and oligodactyly of upper limbs. Her mother has triphalangism of the left thumb and a hypoplastic right thumb with stiff metacarpophalangeal joint. She also has downward-slanting palpebral fissures, malar hypoplasia, and deepset eyes. This observation offers an opportunity to revisit the acrofacial dysostoses syndromes, including Nager-Reynier syndrome, Genée-Wiedeman syndrome, and lethal forms.     

TGFbeta1 enhances formation of cellular Abeta/apoE deposits in vascular myocytes

Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-beta protein (Abeta) in cells exposed to transforming growth factor beta1 (TGFbeta1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in beta-amyloidosis in vivo and produce Abeta in cell culture. We found that cell treatment with TGFbeta1 together with apoE4 strongly increased the amount of cellular Abeta. The intracellular Abeta co-localized with apoE but not with TGFbeta, similarly as in vascular beta-amyloid. Some cellular Abeta/apoE deposits increased in size and persisted in culture even after the TGFbeta1 and apoE4 were removed. The appearance of cellular deposits of Abeta was associated with increased production of the amyloid-beta precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFbeta1 can trigger vascular beta-amyloidosis by inducing intracellular formation of stable Abeta/apoE deposits.     

Responses of nucleus reticularis tegmenti pontis neurons to vestibular stimulation in the rat

Summary Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.Supported by DGRST 79.7.1012     

Antibody avidity: use for the diagnosis of HIV early infection

Determination of IgG avidity is useful to distinguish primary infection from reactivation or reinfection in viral, parasitic or bacterial infections. For diagnosis of HIV type 1 primary infection, the detection of IgM antibodies is often useless since they are also found in chronic infection. The usual serology (Elisa, western-blot, p24 antigen) may present no interest if done too late (more than 2 or 3 months after infection). Therefore, we have developed a test to determine the avidity of anti-HIV1 antibodies, using 1 M guanidine as denaturing agent. We have adapted the measurement of avidity to the Axsym automatic system for a routine use. Indeed, since requests for avidity determinations are sporadic, the use of microplates is not convenient. Using this assay, we found a low avidity (less than 50%) in immunocompetent and recent infected patients (less than 6 months), compared to old infected patients (more than 12 months) who had high avidity (80 to 100%). However, early treated patients (in the 6 months after contamination) had also low avidities but with a slower development of antibody maturation (8 to 27 months versus 2 to 8 months in non treated patients). To conclude, the determination of the anti-HIV1 avidity, according to the proper procedures explained here (notion of treatment and/or serious immunodepression), may help the physician to date the infection in each new infected patient who might benefit from an early treatment.     

Diagnosis ofMycoplasma pneumoniae infection by microparticle aggluination and antibody-capture enzyme-immunoassay

The performance of two new commercial assays for the serological diagnosis ofMycoplasma pneumoniae infection (microparticle agglutination and antibody-capture enzyme-immunoassay) was studied using a panel of 169 serum samples from patients withMycoplasma pneumoniae pneumonia and a control group. Both assays were shown to be sensitive and specific for diagnosis. The performance of the capture immunoassay, however, decreased in older patients, probably due to its inability to detect cases of reinfection without IgM antibody response.     

Coordinate-based versus structural approaches to brain image analysis

A basic issue in neurosciences is to look for possible relationships between brain architecture and cognitive models. The lack of architectural information in magnetic resonance images, however, has led the neuroimaging community to develop brain mapping strategies based on various coordinate systems without accurate architectural content. Therefore, the relationships between architectural and functional brain organizations are difficult to study when analyzing neuroimaging experiments. This paper advocates that the design of new brain image analysis methods inspired by the structural strategies often used in computer vision may provide better ways to address these relationships. The key point underlying this new framework is the conversion of the raw images into structural representations before analysis. These representations are made up of data-driven elementary features like activated clusters, cortical folds or fiber bundles. Two classes of methods are introduced. Inference of structural models via matching across a set of individuals is described first. This inference problem is illustrated by the group analysis of functional statistical parametric maps (SPMs). Then, the matching of new individual data with a priori known structural models is described, using the recognition of the cortical sulci as a prototypical example.     

Fibrillin network in normal bone tissue

The molecular basis for Marfan's syndrome is known to reside in mutations in FBN1, the gene for fibrillin 1. The skeletal manifestations of Marfan syndrome include morphologic abnormalities and osteopenia. Presence and distribution of fibrillin 1 in adult bone (healthy or with Marfan syndrome) has not been studied extensively. We evaluated distribution of fibrillin and type III collagen in bone and cartilage of children and adults without bone disease, using monoclonal antibodies. Fibrillin is mostly present in attachment sites for tendons. In cartilage and bone tissue, fibrillin is identified at the junction between cartilage and bone in children, and in the areas with intense osteoblastic activity. These data suggest participation of fibrillin in bone formation and growth during youth and in bone mineralisation in adult.