doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

MR imaging of posteromedial and posterolateral stabilisers of the knee: anatomic basis and patterns of lesions in knee injuries

Summary The angular points are the ligamentous and tendinous structures that reinforce the posteromedial and posterolateral capsule of the knee and share in fixation of the posterior horns of the menisci. They are often damaged in acute injuries and this is usually associated with ruptures of the cruciate and collateral ligaments and may add to the degree of laxity. We describe the normal appearance of these structures in terms of the sectional anatomy, correlated with the lesional appearances of complete and incomplete ruptures and associated meniscal detachments as shown by clinical testing and arthrotomy findings.

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IRM des points d'angle du genou : bases anatomiques et applications aux genoux traumatiques

Résumé Les points d'angle sont des structures ligamentaires et tendineuses qui renforcent la capsule postéro-médiale et postéro-latérale et participent à la fixation des cornes postérieures des ménisques. Leurs lésions, fréquentes au cours des traumatismes aigus, sont généralement associées à des ruptures des ligaments croisés et des ligaments collatéraux et peuvent être source d'une aggravation de la laxité. Nous rapportons, en corrélation avec l'anatomie en coupe, l'aspect normal de ces structures, et en corrélation avec les données de l'arthrotomie et du testing les aspects lésionnels observés au cours des traumatismes : ruptures complètes, incomplètes et désinsertions méniscales associées.

     

Predictors of low CD4 count in resource-limited settings: based on an antiretroviral-naive heterosexual thai population

A barrier to the appropriate provision of antiretroviral therapy to treat immunosuppressed HIV-infected persons in resource-poor countries is identifying who requires treatment. The World Health Organization (WHO) has suggested using a clinical algorithm combined with a total lymphocyte count (TLC) < 1200 cells/mm as a surrogate for a CD4 count less than 200 cells/mm when it is not possible to measure the CD4 count. We evaluated various TLC levels, anemia, and body mass index and compared our data with the WHO criteria to develop a more sensitive algorithm to predict CD4 counts of < 200 cells/mm and < 350 cells/mm in 839 men and women from Thailand infected with HIV-1 subtype E (CRF01_AE). The December 2003 WHO guidelines had a sensitivity of 34.1% in men and 31.8% in women to detect persons with a CD4 count < 200 cells/mm in this HIV-infected population from Thailand. The use of a TLC < 1500 cells/mm or TLC < 2000 cells/mm combined with anemia or WHO stage II infection doubled the sensitivity to detect persons with a CD4 count < 200 (63.0% in men, 68.2% in women) with less than a 6% decrease in specificity.     

Activation of NR1a/NR2B receptors by soluble factors from APP-stimulated monocyte-derived macrophages: implications for the pathogenesis of Alzheimer's disease

Amyloid-beta peptide (Abeta), the major component of amyloid plaques, can activate brain mononuclear phagocytes (MP; macrophages and microglia), leading to their secretion of neurotoxins. Recent studies strongly suggest that MP-mediated neurotoxicity plays an important role in the pathogenesis of Alzheimer's disease (AD). To further explore this notion, human monocyte-derived macrophages (MDM) were stimulated with naturally secreted alpha-processing soluble amyloid precursor protein/p3 (alphaAPPs/p3) or beta-processing APP/Abeta (betaAPPs/Abeta). MDM conditioned media (MCM) was recovered and tested for its ability to activate recombinant N-methyl-d-aspartate (NMDA) receptor subtype NR1a/NR2B expressed in Xenopus oocytes. Pressure ejection of alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM produced inward currents of 59.5 +/- 8.9 nA (mean +/- S.E.M., n = 31) and 111.1 +/- 21.0 nA (n = 42) in NR1a/NR2B-expressing oocytes, respectively. The MCM-induced currents were concentration dependent and blocked by 50 microM of the NMDA receptor antagonist 2-amino-5-phosphnovalerate, but not by a non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). The alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM placed in non-injected oocytes failed to generate inward current. These results demonstrate that APPs/Abeta-stimulated MCM directly activate NMDA receptor subtypes relevant in the pathogenesis of AD.     

Understanding the psychosocial needs of HIV-positive women: a qualitative study

The purpose of this study was to engage women with HIV disease in a qualitative needs assessment for psychological services. Focus groups/interviews were held to develop an understanding of these women's experiences and perceptions of services needed within a support group format. Results support women's interest in and perceived need for psychosocial group intervention and provide feedback on how to structure groups, including considerations for the facilitator, concrete barriers to address, and attention to group attributes and guidelines. These results support ongoing development of psychosocial support groups for women with HIV disease and further exploration of the efficacy of group models for the diverse subgroups of women with HIV/AIDS.     

Characterization of the Mycobacterium bovis restriction fragment length polymorphism DNA probe pUCD and performance comparison with standard methods

In this study, the newly described Mycobacterium bovis restriction fragment length polymorphism (RFLP) typing probe pUCD was characterized by sequence analysis and the previously observed polymorphic banding pattern was reproduced with a combination of three oligonucleotide probes in a single, mixed hybridization. In addition, the ability of pUCD to distinguish between 299 M. bovis isolates from the Republic of Ireland was assessed in relation to established methods and a statistical function for objective comparison of RFLP probes was derived. It was found that typing with pUCD alone produced greater discrimination between M. bovis isolates than typing with the commonly used mycobacterial DNA probes IS6110, PGRS, and DR and also by the spoligotyping technique. pUCD and DR in combination produced the highest level of discrimination while maintaining a high level of concordance with known epidemiological data relating to the samples. The reduction of pUCD to the level of oligonucleotides should in future allow pUCD and DR to be included together in a mixed hybridization, thus producing a high level of M. bovis strain type discrimination from a single round of RFLP analysis.