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AM Innes KM Boycott EG Puffenberger D Redl IM MacDonald AE Chudley C Beaulieu R Perrier T Gillan A Wade JS Parboosingh 《Clinical genetics》2010,78(5):424-431
Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population. 相似文献
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Paulsson AK McMullen KP Peiffer AM Hinson WH Kearns WT Johnson AJ Lesser GJ Ellis TL Tatter SB Debinski W Shaw EG Chan MD 《中国神经肿瘤杂志》2013,(1):52-52
PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM. 相似文献
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Complete avoidance of breast-feeding is the surest way to avoid mother-to-child transmission (MTCT) of HIV through breast-feeding, but replacement feeding exposes infants, especially those born in developing countries, to the risk of other infectious diseases with consequent increase in morbidity and mortality. One study has suggested that exclusive breast-feeding during the first months of life carries a lower risk of HIV transmission than when other foods are given in addition to breast milk. Other studies have provided limited data on the risks of HIV transmission according to different patterns of breast-feeding, but studies have used different definitions of breast-feeding patterns and have analysed their data with adjustment on different risk factors. This hampers our ability to understand the mechanisms underlying HIV transmission through breast milk and the risks associated with different infant feeding practices. Consequently it is difficult to determine the best interventions to reduce the risk of transmission and the development of optimal policies. In collaboration with research teams involved with infant feeding research, the World Health Organization has developed a tool to assist studies on MTCTto collect information in a standardized manner, using common definitions and terms. The purpose is to facilitate comparisons between studies and the quantification of the risks of transmission according to various feeding patterns, after adjusting for potential confounding variables. The tool includes a core questionnaire to record infant feeding practices and other key information on the mother's and the infant's health. It also provides guidance on methods of analysis and presentation of the complex data on infant feeding. The tool can be used in prospective research studies on MTCT prevention, as well as providing the framework to assess infant feeding patterns in intervention programmes, such as those providing intensive counselling to mothers on infant feeding. The tool will facilitate the compilation of information from these studies which will ultimately provide scientific basis for updating guidelines and policies on infant feeding by mothers infected with HIV. 相似文献
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OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families. 相似文献
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The regulation of hemopoiesis in long-term bone marrow cultures. II. Stimulation and inhibition of stem cell proliferation 总被引:6,自引:1,他引:6
The isolation of a DNA synthesis inhibitor (NBME fraction IV) and stimulator (RBME fraction III) specific for the hemopoietic stem cell (CFU-s) from freshly isolated normal adult and regenerating murine bone marrow, respectively, has been well documented. We have utilized long- term liquid bone marrow cultures in a further analysis of the role of these factors in the regulation of CFU-s proliferation. Our results show that shortly after feeding, at a time when the cultured CFU-s are actively proliferating, high levels of the hemopoietic stem cell proliferation stimulator fraction III can be isolated from the culture medium. In contrast, the presence of essentially noncycling CFU-s found in cultures fed 8-10 days previously correlates with high levels of the hemopoietic stem cell inhibitor fraction IV. These results suggest that a certain balance between these factors determines CFU-s proliferation in the long-term cultures. In support of this, DNA synthesis in actively cycling CFU-s in the long-term cultures is inhibited for at least 3 days by the addition of excess NBME fraction IV (inhibitor). Furthermore, DNA synthesis in noncycling cultured CFU-s is stimulated for at least 5 days by the addition of RBME fraction III (stimulator). 相似文献
50.
Inhibitory synaptogenesis in mouse somatosensory cortex 总被引:4,自引:3,他引:1
It is widely believed that inhibitory synapses are not present or present
in only small numbers in the rodent cerebral cortex during the early
postnatal period when the cortex is being innervated by thalamocortical
fibers. Quantitative electron microscopy was carried out on the
posteromedial barrel subfield of mouse somatosensory cortex from postnatal
day 4 (P4) when thalamocortical innervation of the barrels is becoming
established, through to sexual maturity (>P32), and in adulthood. Both
asymmetrical (putatively excitatory) and symmetrical (putatively
inhibitory) synapses were present in all layers from P4. The symmetrical
synapses were immunoreactive for GABA at all ages. There was a progressive
increase in both asymmetrical and symmetrical synapses up to P32, density
in all layers increasing 16-fold, with the production of asymmetrical
synapses leading and greatly outstripping that of symmetrical. From P32 to
P120, the oldest age studied, synaptic numbers declined by 18% to 13 times
the P4 level, but this affected predominantly layers II/III, IV and V, and
mainly involved asymmetrical synapses. The relative percentage of
asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32
it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that
inhibitory synaptogenesis in the rodent cortex begins earlier than
previously thought, a basis for inhibition being present from the earliest
period. Pruning of all synapses occurs well after thalamocortical
innervation is established and inhibitory synapses are less affected by the
pruning process.
相似文献