北方汉族人群维生素D受体基因Bsm I位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea

We studied the long-term acceptability of nasal continuous positive airway pressure (CPAP) treatment in 168 consecutive patients, 147 with obstructive sleep apnea (OSA) and 21 with snoring. Follow-up was between 1.5 and 78 months. At latest follow-up 107 of 168 (64%) were still using CPAP. Acceptance of CPAP was least for patients with snoring alone (6 of 21 persisted) and best for patients with both excessive daytime somnolence and severe hypoxemia (minimum SaO2 less than 75%), of whom 40 of 45 (89%) persisted with treatment. Patients with excessive daytime somnolence but without severe hypoxemia were less tolerant of CPAP (39 of 71, 55%, persisted) than patients with no symptoms of excessive somnolence but with severe hypoxemia (21 of 30, 70%, persisted). The most common reasons for discontinuing CPAP were intolerance of the mask (26 of 61), the inconvenience of treatment (16 of 61), and the lack of symptomatic benefit from treatment (10 of 61). We concluded that long-term acceptance of CPAP was difficult to predict in advance but that it was most likely in patients with the most severe sleep apnea. Because intolerance of the mask and inconvenience were the most common reasons for ceasing treatment, improvements in the design of CPAP systems and careful patient training may improve the acceptability of CPAP substantially.     

Joint custody: historical, legal, and clinical perspectives with emphasis on the situation in Canada

The search for ways to mitigate the effects of family breakdown on parents and children includes legislative and clinical efforts which to some extent influence each other. In the past year much public interest has been aroused in Canada, and particularly in Ontario, in the issue of legislative changes which would make joint custody the usual or "preferred" legal disposition of custody cases. This paper provides a discussion of the legislated preference, or "rebutable presumption" of joint custody from a historical, legal and clinical point of view. Definition and elaboration of what joint custody is from the legal and practical perspectives is provided with an emphasis on Canadian laws and practice. The legal rights of the non-custodial parent are explained, and relevant case law is highlighted. The relationship between joint custody, support orders and relitigation rates are elaborated. Following this is a critical overview of the empirical research on joint custody as it relates to the adjustment of children and parent satisfaction is included. It is concluded that while there is little question that shared parenting can be beneficial to children, the enthusiasm of legislators for joint custody has not been supported by empirical data. It is necessary to examine under what circumstances and for which kinds of parents and children joint custody might be beneficial since it is unlikely that one solution will fit the needs of all families and all stages of family life.     

Radiation-induced lung injury in vivo: Expression of transforming growth factor—Beta precedes fibrosis

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF), a fibrogenic and radiation-inducible cytokine, was studied from 1–16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF protein in bronchoalveolar lavage (BAL) fluid peaking at 3–6 weeks as compared to sham-irradiated control rats. Steady state TGF mRNA expression as shown by whole lung northern blot assay paralleled the TGF protein expression in BAL fluid. The peak of TGF protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8–10 weeks after irradiation. In conclusion, TGF and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.     

Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy

While an unstable CTG triplet repeat expansion is responsible for myotonic dystrophy, the mechanism whereby this genetic defect induces the disease remains unknown. To detect proteins binding to CTG triplet repeats, we performed bandshift analysis using as probes double- stranded DNA fragments having CTG repeats [ds(CTG)6-10] and single- stranded oligonucleotides having CTG repeats ss(CTG)8 or RNA CUG triplet repeats (CUG)8. The source of protein was nuclear and cytoplasmic extracts of HeLa cells, fibroblasts and myotubes. Proteins binding to the double-stranded DNA repeat [ds(CTG)6-10], were inhibited by nonlabeled ds(CTG)6-10, but not by a non-specific DNA fragment (USF/AD-ML). Another protein binding to ssCTG probe and RNA CUG probe was inhibited by nonlabeled (CTG)8 and (CUG)8. Nonlabeled oligos with different triplet repeat sequences, ss(CAG)8 or ss(CGG)8, did not inhibit binding to the ss(CTG)8 probe. However, when labeled as probes, the (CAG)8 and (CGG)8 bound to proteins distinct from the CTG proteins and binding was inhibited by nonlabeled (CAG)8 or (CGG)8 respectively. The protein binding only to the RNA repeat (CUG)8 was inhibited by nonlabeled (CUG)8 but not by nonlabeled single- or double-stranded CTG repeats. Furthermore, the CUG-BP exhibited no binding to an RNA oligonucleotide of triplet repeats of the same length but having a different sequence, CGG. The CUG binding protein was localized to the cytoplasm, whereas dsDNA binding proteins were localized to the nuclear extract. Thus, several trinucleotide binding proteins exist and their specificity is determined by the triplet sequence. The novel protein, CUG-BP, is particularly interesting since it binds to triplet repeats known to be present in myotonin protein kinase mRNA which is responsible for myotonic dystrophy.      

Serum pregnancy-specific beta1-glycoprotein before embryo transfer is related to endometrial thickness and to outcome prognosis in women undergoing in-vitro fertilization treatment

We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.      

Heminested inverse PCR for IS6110 fingerprinting of Mycobacterium tuberculosis strains.

A heminested inverse PCR (HIP) for the amplification of sequences flanking the Mycobacterium tuberculosis insertion sequence IS6110 has been developed. The method depends upon primers that anneal to IS6110 at sites between its 5' end and the closest BsrFI site. The accuracy of HIP was demonstrated by the amplification of sequences within plasmid constructs carrying one or two copies of the insertion sequence IS986 in different orientations. The identities of the amplicons produced from strains carrying a single copy of IS6110 were verified by nucleotide sequencing. Analyses of 204 M. tuberculosis strains including those involved in outbreaks showed that IS6110 HIP is highly discriminatory and reproducible. HIP fingerprinting of these 204 strains generated 136 distinct types, and its discriminatory power was equivalent to that of standard restriction fragment length polymorphism analysis. The method is therefore of value for the rapid fingerprinting of M. tuberculosis strains for epidemiological purposes.     

Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.