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Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92]-->GGT), predicting Tyr30Arg31-->stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow. 相似文献
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Joachim H. Ix Mary L. Biggs Kenneth Mukamal Luc Djousse David Siscovick Russell Tracy Ronit Katz Joseph A. Delaney Paulo Chaves Dena E. Rifkin Jan M. Hughes-Austin Pranav S. Garimella Mark J. Sarnak Michael G. Shlipak Jorge R. Kizer 《Journal of the American Society of Nephrology : JASN》2015,26(10):2494-2503
Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m2, and median urine PIIINP was 2.6 (interquartile range, 1.4–4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals. 相似文献
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Thirty younger (age 20–30) and 30 older (age 69–85) right-handed Hebrew speakers performed a semantic judgement task while processing literal word pairs and conventional metaphors, presented in the divided visual field paradigm. Older adults responded more accurately to conventional metaphors in the right visual field/left hemisphere versus the left visual field/right hemisphere, whereas younger adults showed no lateralization. Vocabulary scores cancelled group differences in lateralization. An additional lexical decision task replicated the main finding of left-hemisphere lateralization in older but not in younger participants. We suggest that accumulated knowledge increases left-hemisphere lateralization on tasks of language comprehension in older relative to younger adults. 相似文献
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Neurological Sciences - Bradykinesia, dysrhythmia, and decrement in hand movements (HM) are core symptoms of Parkinson’s disease (PD). The maximal rate of repetitive rhythm-preserving HM can... 相似文献
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Daniela Dünn-Kittenplon Asaf Ashkenazy-Titelman Inna Kalt Jean-Paul Lellouche Yaron Shav-Tal Ronit Sarid 《Viruses》2021,13(4)
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’. 相似文献
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J. Halevy M. D. A. Achiron M. D. D. Spiegel M. D. M. Nili M. D. J. Luboshits M. D. Y. Yerushalmi M. D. E. Theodor M. D. 《The American journal of gastroenterology》1990,85(2):210-212
Whereas, in chronic type B hepatitis, the therapeutic effect of alpha-interferon has been studied extensively, data on the effect of interferon on the course and prognosis of acute hepatitis B are scarce in the literature. We report a case of acute type B hepatitis complicated by life-threatening extrahepatic manifestations where recombinant alpha-interferon facilitated clinical, biochemical, and serological recovery. 相似文献