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81.
Jincy Winston Laura Duerden Matthew Mort Ian M Frayling Mark T Rogers Meena Upadhyaya 《European journal of human genetics : EJHG》2015,23(1):67-71
Facioscapulohumeral muscular dystrophy 1 (FSHD1) is caused by a contraction in the number of D4Z4 repeats on chromosome 4, resulting in relaxation of D4Z4 chromatin causing inappropriate expression of DUX4 in skeletal muscle. Clinical severity is inversely related to the number of repeats. In contrast, FSHD2 patients also have inappropriate expression of DUX4 in skeletal muscle, but due to constitutional mutations in SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1), which cause global hypomethylation and hence general relaxation of chromatin. Thirty patients originally referred for FSHD testing were screened for SMCHD1 mutations. Twenty-nine had >11 D4Z4 repeats. SMCHD1 c.1040+1G>A, a pathogenic splice-site variant, was identified in a FSHD1 family with a borderline number of D4Z4 repeats (10) and a variable phenotype (in which a LMNA1 sequence variant was previously described), and SMCHD1 c.2606 G>T, a putative missense variant (p.Gly869Val) with strong in vitro indications of pathogenicity, was identified in a family with an unusual muscular dystrophy with some FSHD-like features. The two families described here emphasise the genetic complexity of muscular dystrophies. As SMCHD1 has a wider role in global genomic methylation, the possibility exists that it could be involved in other complex undiagnosed muscle disorders. Thus far, only 15 constitutional mutations have been identified in SMCHD1, and these two sequence variants add to the molecular and phenotypic spectrum associated with FSHD. 相似文献
82.
Acute graft‐versus‐host disease (GVHD) is a common and serious complication of allogeneic blood and marrow transplantation. Acute GVHD is commonly graded according to modified Glucksberg criteria. There is considerable within‐grade heterogeneity with different patterns of skin, liver, or gut involvement. In this commentary, we provide an analytical review of ambiguities in acute GVHD severity scoring and offer specific proposals meant to generate discussion in the BMT community for adoption, refinement, and where appropriate, validation studies. 相似文献
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Jhalani J Goyal T Clemow L Schwartz JE Pickering TG Gerin W 《Blood pressure monitoring》2005,10(6):317-319
OBJECTIVE: To determine whether elevated clinic blood pressure compared with daytime ambulatory blood pressure, referred to as the white-coat effect, is associated with anxiety and increased blood pressure expectancy in the doctor's office. METHODS: The 24-h ambulatory blood pressure measurements and physicians' blood pressure measurements were obtained in 226 normotensive and hypertensive study participants. Anxiety levels were assessed multiple times during the clinic visit using a Visual Analog Scale. Participants' expectations regarding the clinic visit were assessed using a six-item scale (Expectations of Outcomes Scale). The white-coat effect was computed as the difference between the mean clinic blood pressure and the mean daytime ambulatory blood pressure. Multiple regression analysis was performed to examine the association between anxiety, outcome expectations and the white-coat effect, adjusting for age, sex, and ambulatory blood pressure level. RESULTS: As predicted, outcome expectations and anxiety during the clinic visit were significantly associated with the white-coat effect. Results of the regression analysis indicated that only expectancy had an independent effect on the systolic white-coat effect; however, both anxiety and expectancy had independent effects on the diastolic white-coat effect. CONCLUSION: Our results provide empirical support to the hypothesis that anxiety and blood pressure expectancy may elevate clinic blood pressure. 相似文献
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Agalactosyl IgG: an aid to differential diagnosis in early synovitis 总被引:10,自引:0,他引:10
A Young N Sumar K Bodman S Goyal H Sinclair I Roitt D Isenberg 《Arthritis and rheumatism》1991,34(11):1425-1429
Sixty consecutive patients presenting with early-onset synovitis were studied by measuring rheumatoid factor (RF) titers and the percentage of oligosaccharide chains attached to the C gamma 2 domain of IgG that lack galactose (GAL[0]). After 2 years of followup, 39 patients (65%) had developed rheumatoid arthritis (RA), and 21 had developed a variety of other inflammatory joint diseases. A combination of RF positivity and GAL(0) levels above the age-corrected mean gave a positive predictive value for a diagnosis of RA in 94% of these patients. These observations may well have clinical utility. 相似文献
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