Use of nonviral vectors for cystic fibrosis gene therapy

Over the last decade, three groups within the United Kingdom (Edinburgh, Oxford, and Imperial College, London) have undertaken key studies in the development of clinical gene therapy for cystic fibrosis. In 2001, catalyzed by the Cystic Fibrosis Trust, these groups came together to form the United Kingdom Cystic Fibrosis Gene Therapy Consortium. The Consortium has removed duplication and competition, developed core facilities playing to the respective strengths of the centers, and introduced the joint strategy described in this article. This is driven by a clinical trial program, with a product pipeline and the necessary development of novel preclinical and human assays. The program is milestone-related, has a structure that lies between the pharmaceutical industry and academia, and has as its endpoint negotiations with industry to undertake a phase III clinical trial of the identified product.     

Prediction of perinatal outcome in fetuses suspected to have intrauterine growth restriction: Doppler US study of fetal cerebral, renal, and umbilical arteries

PURPOSE: To determine and compare the diagnostic performance of fetal middle cerebral (MCA), renal (RA), and umbilical (UA) arterial Doppler ultrasonography (US) for prediction of adverse perinatal outcome in suspected intrauterine growth restriction (IUGR). MATERIALS AND METHODS: Two hundred ninety-three small-for-gestational age fetuses (24-39 weeks at recruitment and US-estimated weight or abdominal circumference below 10th percentile) were prospectively examined with Doppler US of the UA, MCA, and RA. Clinicians were blinded to MCA and RA Doppler measurements. RESULTS: Seventy-six fetuses (25.9%) had at least one major or minor adverse perinatal outcome. Major outcomes included stillbirth, neonatal death, neurologic complication, and necrotizing enterocolitis. The MCA pulsatility index (PI), compared with the UA PI and RA PI, was more sensitive (72.4% vs 44.7% and 8.3%) but less specific (58.1% vs 86.6% and 92.6%) in predicting adverse outcome. The UA PI had the highest positive likelihood ratio (ratio, 3.3); the MCA PI had the lowest negative likelihood ratio (ratio, 0.48). When gestational age at the first Doppler US examination was less than 32 weeks, the MCA PI had a sensitivity of 95.5% and negative predictive value of 97.7% for major adverse outcome (negative likelihood ratio, 0.10). CONCLUSION: In suspected IUGR, while an abnormal UA PI is a better predictor of adverse perinatal outcome than an abnormal MCA or RA PI, a normal MCA PI may help to identify fetuses without major adverse perinatal outcome, especially before 32 weeks gestational age.     

Expression of the human NOV gene in first trimester fetal tissues

NOV, located on human chromosome 8q24.1, was originally cloned following discovery of its avian homolog as a consequence of over-expression in virally induced nephroblastoma. The gene product is a secreted, modular, protein and a member of the CCN gene family. Evidence to date indicates that the expression of the wild type protein is associated with cellular quiescence in normal embryonic fibroblasts yet produces growth stimulatory effects on established murine NIH 3T3 cells. Here we report the expression of NOV in the first trimester of human embryogenesis, between 5 and 10 weeks. In situ hybridisation and immunohistochemistry reveal widespread expression in derivatives of all three germ layers. The most abundant sites of expression are in the motor neurons and floor plate of the spinal cord, adrenal cortex, fusing skeletal, and smooth muscle, the urogenital system and the developing heart. Additionally, expression is seen in the cranial ganglia, differentiating chondrocytes, gonads, and lung. The sites of expression suggest strongly that autocrine or paracrine expression of NOV is associated with the process of cell differentiation.     

Sonographic Diagnosis of Chronic Abruption

BackgroundPlacental abruption is usually an acute event in which clinical decision-making overrides the need for ultrasound imaging. By contrast, chronic abruption may present with vague or even confusing clinical findings. We describe a case in which the diagnosis of chronic abruption was established by ultrasound and the findings directly influenced clinical care.CaseA 30-year-old woman with asymptomatic preeclampsia was evaluated in our fetal medicine unit at 30 weeks’ gestation. Despite normal fetal monitoring, a large, retroplacental sonolucent area was noted on ultrasound. A planned Caesarean section was performed two days later, despite normal daily fetal monitoring, because the mass had increased in size. Placental pathology confirmed the diagnosis of chronic abruption.ConclusionUltrasound may establish the diagnosis of a large chronic placental abruption that is relevant for clinical management.     

内源性一氧化碳在生殖系统中作用的研究

内源性一氧化碳(endogenous CO)主要由血红素加氧酶(hemeoxygenase,HO)催化分解血红素而产生,是继一氧化氮之后发现的另一种具有重要生物学效应的气体分子,广泛参与体内的各种生理和病理过程,在心血管系统、神经系统、消化系统中起非常重要的作用。近年来,其在生殖系统的研究也日益受到重视。在女性生殖系统,HO/CO不仅会影响动情周期、分娩和哺乳行为,而且会抑制受孕子宫肌层的收缩,参与保护作用。而在男性生殖系统,HO/CO能够通过抗炎、抗氧化以及抗凋亡机制保护睾丸免受应激的损伤。这种可诱导的保护性作用将成为研究的新热点。     

Number and timing of antenatal HIV testing: Evidence from a community-based study in Northern Vietnam

Background  

HIV testing for pregnant women is an important component for the success of prevention of mother-to-child transmission of HIV (PMTCT). A lack of antenatal HIV testing results in loss of benefits for HIV-infected mothers and their children. However, the provision of unnecessary repeat tests at a very late stage of pregnancy will reduce the beneficial effects of PMTCT and impose unnecessary costs for the individual woman as well as the health system. This study aims to assess the number and timing of antenatal HIV testing in a low-income setting where PMTCT programmes have been scaled up to reach first level health facilities.     

Differential distributions of red-green and blue-yellow cone opponency across the visual field

The color vision of Old World primates and humans uses two cone-opponent systems; one differences the outputs of L and M cones forming a red-green (RG) system, and the other differences S cones with a combination of L and M cones forming a blue-yellow (BY) system. In this paper, we show that in human vision these two systems have a differential distribution across the visual field. Cone contrast sensitivities for sine-wave grating stimuli (smoothly enveloped in space and time) were measured for the two color systems (RG & BY) and the achromatic (Ach) system at a range of eccentricities in the nasal field (0-25 deg). We spatially scaled our stimuli independently for each system (RG, BY, & Ach) in order to activate that system optimally at each eccentricity. This controlled for any differential variations in spatial scale with eccentricity and provided a comparison between the three systems under equivalent conditions. We find that while red-green cone opponency has a steep decline away from the fovea, the loss in blue-yellow cone opponency is more gradual, showing a similar loss to that found for achromatic vision. Thus only red-green opponency, and not blue-yellow opponency, can be considered a foveal specialization of primate vision with an overrepresentation at the fovea. In addition, statistical calculations of the level of chance cone opponency in the two systems indicate that selective S cone connections to postreceptoral neurons are essential to maintain peripheral blue-yellow sensitivity in human vision. In the red-green system, an assumption of cone selectivity is not required to account for losses in peripheral sensitivity. Overall, these results provide behavioral evidence for functionally distinct neuro-architectural origins of the two color systems in human vision, supporting recent physiological results in primates.