The domain encoded by exon 2 of the survival motor neuron protein mediates nucleic acid binding [published erratum appears in Hum Mol Genet 1998 Oct;7(11):1831]

Spinal muscular atrophy (SMA) is a motor neuron disorder resulting from anterior horn cell death. Survival motor neuron ( SMN ) is the SMA- determining gene and is deleted or gene converted in >95% of SMA patients. The SMN protein has a role in spliceosomal snRNP biogenesis and has therefore been implicated indirectly in general cellular RNA processing due to its unique sub-nuclear localization within structures termed 'gems', which co-localize with spliceosomal factors within coiled bodies. In this report, direct SMN RNA-binding activity, in addition to ssDNA and dsDNA binding is demonstrated. The region of SMN encoded by exon 2 is necessary and sufficient to mediate its nucleic acid-binding activities. This domain is homologous to several nucleic acid-binding factors, including several high mobility group (HMG) proteins. Additionally, previously reported SMN missense mutations isolated from SMA patients demonstrated reduced RNA-binding activity, suggesting that nucleic acid binding is functionally significant.      

Child sexual abuse in southern Brazil and associated factors: a population-based study

Background  

The prevalence of child sexual abuse (CSA) in the population has been poorly described in developing countries. Population data on child sexual abuse in Brazil is very limited. This paper aims to estimate lifetime prevalence of child sexual abuse and associated factors in a representative sample of the population aged 14 and over in a city of southern Brazil.     

Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study

The objective of the present study was to assess the efficacy of bisoprolol in migraine prophylaxis. A double-blind placebo-controlled study was conducted in 226 patients with migraine with or without aura, a migraine history of at least 2 years and at least 3 documented attacks during the 28 days run-in period. The duration of treatment was 12 weeks following an initial 28 days' run-in period. Patients reported the number of attacks and their severity in a diary. Treatment with bisoprolol 5 mg resulted in a significant reduction in the frequency of migraine attacks (39% vs 22%) compared to placebo treatment ( p <0.05). Treatment had no effect on the duration and severity of the attacks. Bisoprolol was well tolerated.     

Quantitative hepatitis B virus DNA assessment by the limiting-dilution polymerase chain reaction in chronic hepatitis B patients: evidence of continuing viral suppression with longer duration and higher dose of lamivudine therapy

Lamivudine, a novel cytosine analogue, exhibits potent antiviral activity against hepatitis B virus (HBV) in vitro and in vivo . The standard HBV DNA hybridization assay used in phase II clinical studies has a low sensitivity, the detection limit of HBV DNA levels being ≈ 10⁷ genome equivalents per ml (geq ml^–1). In this work we used a semiquantitative polymerase chain reaction (PCR) assay (detection limit ≈ 10³ geq ml^–1) to determine HBV DNA levels during a 24-week study of lamivudine in 51 stable chronic hepatitis B patients who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Patients were randomly allocated to receive oral doses of 25, 100 or 300 mg lamivudine once daily. At week 24 the median serum concentration of HBV DNA had fallen from 10⁸ to 10⁴ geq ml^–1, a 4-log median reduction. A trend towards more profound suppression of viral replication with an increased dose of lamivudine was observed. After 12 weeks of therapy, 12% of patients had an HBV DNA level that was undetectable in the PCR assay; this increased to 26% after 24 weeks, while in an additional 20% of patients, HBV DNA decreased to the level of detection of the PCR assay. We conclude that a 24-week course of lamivudine decreases serum HBV DNA to the level of PCR detection in 46% of patients. Such additional viral suppressive activity with higher doses and more protracted lamivudine may be of clinical utility prior to liver transplantation. Further studies are needed to define the degree of virus suppression required in clinical practice, and methods are required to increase the efficacy of virus suppression.     

强啡肽A(1-17)在脊髓的致瘫作用及其与神经毒作用的相关性

在以行为学为观察指标(甩尾镇痛和斜板实验)的基础上,用组织学方法探讨大剂量强啡肽A在脊髓水平的致瘫作用与其神经毒作用的关系。结果表明,给大鼠蛛网膜下腔(it)注射强啡肽A(1-17)20nmol·L^-1,共10μl,给药后5～10min即引起大鼠后肢不可逆性瘫痪、甩尾反射被抑制长达40h以上。大鼠脊髓组织学检查发现,腰、骶段脊髓前角运动神经元大量坏死或严重变性、以腰段损伤最为显著(运动神经元减少87.2%),其次是骶段(减少69.6%),胸段损伤不明显(减少8.2%)。     

Human immunodeficiency virus (HIV) antibodies detected by new assays that are enhanced for HIV-1 subtype O

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype O infections are not reliably detected by commonly used anti-HIV-1/2 screening assays. Therefore, anti-HIV-1/2 assays have been modified to increase their sensitivity in detecting antibodies to HIV-1 subtype O. STUDY DESIGN AND METHODS: Two new anti-HIV-1/2 enzyme-linked immunosorbent assays (ELISAs) (Abbott Plus and Ortho Enhanced) were compared with a currently used anti-HIV-1/2 ELISA (Abbott Recombinant) in various serum panels: 91 Western blot-confirmed anti-HIV-1-positive samples, 20 samples from Western blot-confirmed HIV-1-infected patients in log3 serial dilutions, and 1463 samples from consecutive, volunteer, nonremunerated blood donors. RESULTS: Among 91 anti-HIV-1 Western blot- positive samples, 2 (2.2%) were missed by the Abbott Recombinant ELISA, but all 91 were detected by the Abbott Plus and Ortho Enhanced ELISAs. In contrast, two discrepant samples were found to react in viral lysate- based assays. In serial dilutions, Ortho Enhanced ELISA was significantly less sensitive than the Abbott Recombinant and Abbott Plus ELISAs, with the latter two being of comparable sensitivity. The specificities of Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs in 1463 blood donors were 100, 99.93, and 99.86 percent, respectively. Routine testing of 29,102 donations with the enhanced Abbott Plus ELISA revealed a specificity of 99.93 percent. CONCLUSION: Two Western blot-confirmed anti-HIV-1-positive samples were missed by the Abbott Recombinant ELISA but detected by the Abbott Plus and Ortho Enhanced ELISAs. The analytic sensitivity of the Ortho Enhanced ELISA was inferior to that of both Abbott ELISAs. The specificities of the Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs were comparable.     

Invasive pneumococcal infections in Canadian children, 1998-2003: implications for new vaccination programs

BACKGROUND: We conducted active surveillance for invasive pneumococcal disease to assess the serotype and antibiotic resistance patterns in Canada prior to universal infant immunization programs, in most provinces. METHODS: Active surveillance was conducted by the 12 centres of the Canadian Paediatric Society's Immunization Monitoring Program, Active (IMPACT). This report includes children 16 years of age and younger with S. pneumoniae isolated from a normally sterile site, in 1998-2003. RESULTS: During six years of surveillance, 1,868 eligible cases were reported. The 7-valent pneumococcal conjugate vaccine (PCV7) matched 79% of isolates, including 84% from 6-23 month olds and 80% from 2-5 year olds. The proportion of isolates matched by PCV7 significantly decreased over the surveillance period from 81% in 1998 to 73% in 2003 (p = 0.005). The 23-valent polysaccharide vaccine (PPS) matched 90% of isolates from children 2 years or older. Penicillin non-susceptibility rate was stable at 16% of isolates. Cefotaxime/ceftriaxone resistance rate was 5% and limited to penicillin-resistant isolates. Serotypes found in PCV7 accounted for 89% of penicillin-resistant isolates (100% including cross-reacting types 6A and 19A). CONCLUSION: PCV7 matched three quarters of the isolates from young children as immunization programs began; therefore some program failures are inevitable. Children > or =5 years with predisposing conditions need the broader protection of 23-valent PPS vaccine and special attention from providers to ensure receipt. The rate of penicillin resistance remained steady over the last six years. The majority of isolates non-susceptible to penicillin are found in PCV7.