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51.
Anne Frühmesser Jonathon Blake Edda Haberlandt Bianka Baying Benjamin Raeder Heiko Runz Ana Spreiz Christine Fauth Vladimir Benes Gerd Utermann Johannes Zschocke Dieter Kotzot 《European journal of human genetics : EJHG》2013,21(10):1177-1180
Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability. 相似文献
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53.
Roel S. Driessen Wijnand J. Stuijfzand Pieter G. Raijmakers Ibrahim Danad James K. Min Jonathon A. Leipsic Amir Ahmadi Jagat Narula Peter M. van de Ven Marc C. Huisman Adriaan A. Lammertsma Albert C. van Rossum Niels van Royen Paul Knaapen 《Journal of the American College of Cardiology》2018,71(5):499-509
Background
Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity.Objectives
This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively.Methods
Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR.Results
Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively).Conclusions
PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity. 相似文献54.
Sumatriptan Iontophoretic Transdermal System Reduces Treatment‐Emergent Nausea and Is Effective in Patients With and Without Nausea at Baseline – Results From a Randomized Controlled Trial
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55.
Christian Grov Aaron S. Breslow H. Jonathon Rendina Ana Ventuneac 《AIDS and behavior》2014,18(11):2172-2177
In 2007, the New York City (NYC) Department of Health introduced the ‘NYC Condom’—a Lifestyles® condom with a ‘NYC’ logo. Few studies have evaluated attitudes toward or distribution of the ‘NYC Condom’ among men who have sex with men (MSM)—a population at increased risk for HIV/STIs. 148 MSM completed a survey about their exposure to, use of, and experiences using the ‘NYC Condom.’ The majority (93.2 %) had seen the ‘NYC Condom;’ 82.4 % of said men had used it. Among MSM who used it, 82.1 % rated it average or above. Exposure did not statistically differ by race/ethnicity, HIV status, gay or barebacker identification, or sex role. Use was neither significantly associated with demographic characteristics nor recruitment source, suggesting distributional success in reaching various sub-populations of MSM. Among those who had not used the ‘NYC Condom,’ 22.2 % reported size or quality concerns, suggesting a demand for alternative prevention campaigns. 相似文献
56.
Stephen A. Schumacher Jonathon Yardley Alicia L. Bertone 《Drug testing and analysis》2019,11(3):455-460
Magnesium sulfate (MgSO4) was administered to calm competition horses. We evaluated the impact of regulatory requirements for the handling of blood samples on plasma ionized magnesium (iMg), ionized calcium (iCa), the iMg to iCa ratio, and pH. We hypothesized that iCa, iMg. and iMg/iCa would be similar among storage and collection methods. Four blood samples were collected from each of 50 horses on the same day: Group 1 – collection in a heparinized syringe and processed within hours in a clinical laboratory; Group 2 – collection into a plasma separator tube (PST) centrifuged just prior to analysis, and plasma processed as in (1); Group 3 – collection into a PST, refrigerated, shipped via overnight carrier to the United States Equestrian Federation (USEF) Equine Drug Testing and Research laboratory, centrifuged just prior to analysis, and plasma processed; and Group 4 – as in Group 3, but stored frozen at ?80°C for 90 days, thawed, and plasma processed as in Group 3. Results for iMg/iCa are unit‐less, adjusted iMg for potential influence of plasma protein and iCa, and highly correlated with iMg pH (r = ?.933; P < 0.01). Samples processed immediately in a clinical reference laboratory had the greatest iMg/iCa. Both iMg/iCa and pH predictably decreased after freezing (P < 0.001). These data suggest that the iMg/iCa mirrors alterations in iMg regardless of storage and collection methods. This understanding can facilitate the development of a regulatory threshold for the control of the nefarious use of magnesium sulfate in competing horses, and an understanding of potential changes to iMg/iCa with storage of B samples. 相似文献
57.
58.
Willis MS Homeister JW Rosson GB Annayev Y Holley D Holly SP Madden VJ Godfrey V Parise LV Bultman SJ 《Circulation research》2012,111(5):e111-e122
Rationale: Mating type switching/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes utilize either BRG1 or BRM as a catalytic subunit to alter nucleosome position and regulate gene expression. BRG1 is required for vascular endothelial cell (VEC) development and embryonic survival, whereas BRM is dispensable. Objective: To circumvent embryonic lethality and study Brg1 function in adult tissues, we used conditional gene targeting. To evaluate possible Brg1-Brm redundancy, we analyzed Brg1 mutant mice on wild-type and Brm-deficient backgrounds. Methods and Results: The inducible Mx1-Cre driver was used to mutate Brg1 in adult mice. These conditional-null mutants exhibited a tissue-specific phenotype and unanticipated functional compensation between Brg1 and Brm. Brg1 single mutants were healthy and had a normal lifespan, whereas Brg1/Brm double mutants exhibited cardiovascular defects and died within 1 month. BRG1 and BRM were required for the viability of VECs but not other cell types where both genes were also knocked out. The VEC phenotype was most evident in the heart, particularly in the microvasculature of the outer myocardium, and was recapitulated in primary cells ex vivo. VEC death resulted in vascular leakage, cardiac hemorrhage, secondary death of cardiomyocytes due to ischemia, and ventricular dissections. Conclusions: BRG1-catalyzed SWI/SNF complexes are particularly important in cardiovascular tissues. However, in contrast to embryonic development, in which Brm does not compensate, Brg1 is required in adult VECs only when Brm is also mutated. These results demonstrate for the first time that Brm functionally compensates for Brg1 in vivo and that there are significant changes in the relative importance of BRG1- and BRM-catalyzed SWI/SNF complexes during the development of an essential cell lineage. 相似文献
59.
Lu J Sun Y Nombela-Arrieta C Du KP Park SY Chai L Walkley C Luo HR Silberstein LE 《Experimental hematology》2012,40(4):307-17.e3
Hematopoietic stem cells (HSCs) reside in complex bone marrow microenvironments, where niche-induced signals regulate hematopoiesis. Focal adhesion kinase (Fak) is a nonreceptor protein tyrosine kinase that plays an essential role in many cell types, where its activation controls adhesion, motility, and survival. Fak expression is relatively increased in HSCs compared to progenitors and mature blood cells. Therefore, we explored its role in HSC homeostasis. We have used the Mx1-Cre-inducible conditional knockout mouse model to investigate the effects of Fak deletion in bone marrow compartments. The total number as well as the fraction of cycling Lin(-)Sca-1(+)c-kit(+) (LSK) cells is increased in Fak(-/-) mice compared to controls, while hematopoietic progenitors and mature blood cells are unaffected. Bone marrow cells from Fak(-/-) mice exhibit enhanced, long-term (i.e., 20-week duration) engraftment in competitive transplantation assays. Intrinsic Fak function was assessed in serial transplantation assays, which showed that HSCs (Lin(-)Sca-1(+)c-kit(+)CD34(-)Flk-2(-) cells) sorted from Fak(-/-) mice have similar self-renewal and engraftment ability on a per-cell basis as wild-type HSCs. When Fak deletion is induced after engraftment of Fak(fl/fl)Mx1-Cre(+) bone marrow cells into wild-type recipient mice, the number of LSKs is unchanged. In conclusion, Fak inactivation does not intrinsically regulate HSC behavior and is not essential for steady-state hematopoiesis. However, widespread Fak inactivation in the hematopoietic system induces an increased and activated HSC pool size, potentially as a result of altered reciprocal interactions between HSCs and their microenvironment. 相似文献
60.
Percutaneous management of valvular heart disease is becoming a reality, with multicenter trials supporting minimally invasive procedures for both aortic and mitral valve disease. Historically, the treatment of choice has been aortic valve replacement with conventional surgery for patients with severe aortic stenosis, as the prognosis of untreated patients is poor, particularly if the patient is symptomatic. Transcatheter aortic valve replacement is now available as a minimally invasive option to treat select high-risk patients with severe aortic stenosis. At present more than 30,000 procedures have been performed worldwide, mostly confined to patients at high surgical risk. The short- and medium-term outcomes have been promising. 相似文献