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排序方式: 共有2207条查询结果,搜索用时 15 毫秒
61.
Charlotte W Ockeloen Marjolein H Willemsen Sonja de Munnik Bregje WM van Bon Nicole de Leeuw Aad Verrips Sarina G Kant Elizabeth A Jones Han G Brunner Rosa LE van Loon Eric EJ Smeets Mieke M van Haelst Gijs van Haaften Ann Nordgren Helena Malmgren Giedre Grigelioniene Sascha Vermeer Pedro Louro Lina Ramos Thomas JJ Maal Celeste C van Heumen Helger G Yntema Carine EL Carels Tjitske Kleefstra 《European journal of human genetics : EJHG》2015,23(9):1270-1185
Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases. 相似文献
62.
Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium 总被引:12,自引:0,他引:12
van Hinsbergh VW; Bertina RM; van Wijngaarden A; van Tilburg NH; Emeis JJ; Haverkate F 《Blood》1985,65(2):444-451
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. 相似文献
63.
In vivo T‐cell depletion using alemtuzumab in family and unrelated donor transplantation for pediatric non‐malignant disease achieves engraftment with low incidence of graft vs. host disease
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B. W. Bigger H. Lee A. Logan K. Poulton S. Hughes A. J. Turner D. K. Bonney R. F. Wynn 《Pediatric transplantation》2015,19(2):211-218
In vivo T‐cell depletion, using alemtuzumab therapy prior to SCT, can reduce the incidence of GVHD. This treatment has a potential to delay immune reconstitution resulting in increased morbidity due to viral illnesses. We retrospectively analyzed data on all pediatric patients with non‐malignant disorders who received alemtuzumab‐based conditioning regimens in our center over the last 10 yr (n = 91). Our data show an OS of 91.2%. The incidence of acute (grade 2–4) GVHD was 18.7% and that of chronic GVHD 5.5%. Viremia due to adenovirus, EBV and CMV was seen in 19.8%, 64.8% and 39.6% patients, respectively, with only two deaths attributed to viral infection (adenovirus). Chimerism level at three month was predictive of graft outcome. Nine patients, who had graft failure after first SCT, were salvaged with a second SCT using RIC and same donor (if available). Based on these results, we conclude that the use of in vivo T‐cell depletion is safe, achieves good chimerism and does not lead to increased morbidity and mortality due to viral infections. It is associated with a reduced incidence of chronic GVHD. 相似文献
64.
TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13) 总被引:1,自引:0,他引:1
Wlodarska I; Mecucci C; Marynen P; Guo C; Franckx D; La Starza R; Aventin A; Bosly A; Martelli MF; Cassiman JJ 《Blood》1995,85(10):2848-2852
A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes. 相似文献
65.
Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated 总被引:3,自引:0,他引:3
Billheimer JT Dicker IB Wynn R Bradley JD Cromley DA Godonis HE Grimminger LC He B Kieras CJ Pedicord DL Spitz SM Thomas BE Zolotarjova NI Gorko MA Hollis GF Daly RN Stern AM Seiffert D 《Blood》2002,99(10):3540-3546
Glycoprotein (GP) IIb/IIIa antagonists are effective therapeutic agents, but elicit thrombocytopenia with a frequency that approaches 2%. Here, we provide evidence that thrombocytopenia in humans treated with the GP IIb/IIIa antagonist roxifiban is immune mediated. Two patients underwent conversion to a highly positive drug-dependent antibody (DDAB) status temporally associated with thrombocytopenia. Despite the continued presence of DDABs, the fall in platelet count was reversed by discontinuation of drug treatment, pointing to the exquisite drug dependency of the immune response. DDABs appear to bind to neoepitopes in GP IIb/IIIa elicited on antagonist binding. This information was used to develop an enzyme-linked immunosorbent assay (ELISA) for DDAB using solid-phase GP IIb/IIIa. A high level of specificity is indicated by the observation that DDAB binding is dependent on the chemical structure of the GP IIb/IIIa antagonist and that only 2% to 5% of human blood donors and 5% of chimpanzees present with pre-existing DDABs. Furthermore, none of 108 nonthrombocytopenic patients from the phase II roxifiban study showed an increase in antibody titer. Absorption of thrombocytopenia plasma with platelets reduced the DDAB ELISA signal, indicating that the test detects physiologically relevant antibodies. Screening patients for pre-existing or increasing DDAB titer during treatment with GP IIb/IIIa antagonists may reduce the incidence of drug-induced thrombocytopenia. 相似文献
66.
Intrathoracic lymphoblastic lymphoma (LBL) is classically of T‐cell lineage, but these cases of pleural B‐cell LBL suggest that this is not always the case. Despite the clinical challenges involved every attempt should be made to secure a biopsy and histological diagnosis, as we move into an era of lineage‐directed therapies. 相似文献
67.
Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men. 总被引:8,自引:0,他引:8
C Walton I F Godsland A J Proudler C V Felton V Wynn 《The Journal of clinical endocrinology and metabolism》1992,75(1):170-175
The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion. 相似文献
68.
David Crook Raymond Bruce Melek Worthington Dayid Mulcahy MRCP David Patterson FRCP Victor Wynn FRCP 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1992,6(6):633-639
Summary Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL2 17%; HDL3 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin. 相似文献
69.
An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose. 总被引:1,自引:0,他引:1
C Walton I F Godsland A J Proudler C V Felton V Wynn 《Metabolism: clinical and experimental》1992,41(11):1210-1214
Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age-related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides. 相似文献
70.
Stavros M Stivaros Robert Alston Neville B Wright Kate Chandler Denise Bonney Robert F Wynn Andrew M Will Maqsood Punekar Sean Loughran John-Paul Kilday Detlev Schindler Leena Patel Stefan Meyer 《The British journal of radiology》2015,88(1056)