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931.
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Mutational analysis and expression studies of the neurofibromatosis type 2 (NF2) gene in a patient with a ring chromosome 22 and NF2 总被引:2,自引:0,他引:2
H. Kehrer-Sawatzki Martin Udart Winfrid Krone Reinhard Baden Raimund Fahsold Gilles Thomas Beatrice Schmucker Günter Assum 《Human genetics》1997,100(1):67-74
The case of a seriously disabled and retarded female patient with neurofibromatosis type 2 (NF2) is reported. She suffered
from bilateral vestibular schwannomas, multiple intracranial meningiomas and neurinomas. The constitutional karyotype of the
patient was 46,XX, r(22)/45,XX,–22. A constitutional G to A transition in the proximal 3′ untranslated region of isoforms
1 and 2 was identified in the patient’s NF2 gene and shown not to affect differential splicing or mRNA stability. The instability
of the ring chromosome 22 with the associated loss of tumor suppressor genes on chromosome 22, in particular the loss of the
NF2 gene, are assumed to have caused multiple tumorigenesis in this patient
Received: 7 February 1997 / Accepted: 26 February 1997 相似文献
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A detailed, AMS 14C-dated, pollen record from Cooney Lough, a small lake in Co. Sligo, western Ireland, is presented. Fluctuations in the pollen curves, indicative of changes in pollen productivity and shifts in woodland composition, suggest that the period spanned by the record (9.4–6 ka) was characterised by considerable climate instability. In all, five climate anomalies are recognised (CA-1 to CA-5). The most pronounced anomaly, CA-3, is dated to 8.45–8.2 ka, with the high point of that anomaly (CA-3b) centred on 8.2 ka and lasting about a century. On the basis of age, and also intensity and structure, CA-3b is equated with the 8.2 ka event as recorded in many proxies and especially the Greenland ice-core δ18O records. Key features of the event as recorded in the lake sediments include increased representation of Betula and Pinus (birch and pine; both widely recognised as cold tolerant trees) and a decline in Corylus and also Quercus (hazel and oak; both thermophilous). The anomalies CA-1 and CA-2 precede the 8.2 ka event, the former corresponding probably to the 9.2 ka event and the latter more pronounced, centred on ca. 8.8 ka and with a duration of approximately 100 years. The CA-4 event, at ca. 7.5 ka, is relatively minor as regards intensity while CA-5, which began at ca. 7.1 ka, initiated what seems to be a more long-lasting shift towards cooler conditions. The relationship of these developments to the arrival and expansion of alder (Alnus), a key feature of the Boreal/Atlantic transition in European, including Irish pollen records is also discussed. 相似文献
938.
Philipp A. Gerber Christoph Thalhammer Christian Schmied Silviana Spring Beatrice Amann-Vesti Giatgen A. Spinas Kaspar Berneis 《PloS one》2013,8(8)
The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years. sdLDL particles were determined by gradient gel electrophoresis. Insulin resistance was estimated by using the homeostatic model assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age 63.0 ± 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased in the whole cohort during follow-up. The change in IMT was predicted by the proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in HOMA2 correlated with the proportion of sdLDL particles and changes in this proportion, respectively (p<0.05 for both). Serum resistin levels increased in parallel with the increasing sdLDL particle number, while serum adiponectin increased only in patients with unaltered sdLDL particle number at follow-up (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles and changes in this proportion are predictive of changes in intima media thickness and insulin resistance, and are closely associated with other determinants of an adverse metabolic status. Thus, this parameter extends the individual risk assessment beyond the limitations of traditional risk markers in patients with dysglycemia. 相似文献
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Simon W?hrle Andreas Weiss Moriko Ito Audrey Kauffmann Masato Murakami Zainab Jagani Anne Thuery Beatrice Bauer-Probst Flavia Reimann Christelle Stamm Astrid Pornon Vincent Romanet Vito Guagnano Thomas Brümmendorf William R. Sellers Francesco Hofmann Charles W. M. Roberts Diana Graus Porta 《PloS one》2013,8(10)
Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs. 相似文献