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排序方式: 共有154条查询结果,搜索用时 15 毫秒
1.
Kerry E. Goetz Melissa J. Reeves Shaina Gagadam Delphine Blain Chelsea Bender Cara Lwin Amelia Naik Santa J. Tumminia Robert B. Hufnagel 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(3):828-837
Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community. 相似文献
2.
B M B?cklin A Gessbo M Forsberg A Shokrai B Rozell W Engstr?m 《Journal of clinical pathology》1998,51(1):43-47
AIM: To study how polychlorinated biphenyls (PCBs) affect fetal growth and the expression of the insulin-like growth factor (IGF II) gene in the mink (Mustela vision). METHODS: Ten female mink were each exposed to 0.65 or 1.3 mg Clophen A50/day, respectively, during the reproductive season. The numbers and sizes of viable fetuses were recorded. The expression of the IGF II gene was studied by northern blotting using a mink specific IGF II cDNA probe. RESULTS: The number of viable fetuses decreased after PCB exposure in a dose dependent fashion. Expression of the IGF II gene in adult livers from PCB exposed animals was decreased, compared with control animals, in a dose dependent fashion. In contrast, IGF II expression in placentas and fetuses was unaltered. Furthermore, the maternal excretion of urinary cortisol increased in both exposed groups during the implantation period. CONCLUSIONS: Expression of the IGF II gene is downregulated by PCB exposure in the adult liver. There is also an indication that the regulation of the expression of this gene differs between adult and fetal life. 相似文献
3.
Katherine A. Lygrisse Stephen Zak Vivek Singh Lorraine H. Hutzler Ran Schwarzkopf Joshua C. Rozell 《The Journal of arthroplasty》2021,36(3):833-836
BackgroundAs the Center for Medicare and Medicaid (CMS) moves toward bundled payment plans for total joint arthroplasty (TJA), it becomes necessary to reduce factors that increase cost for an episode of care such as readmissions. The goal of this study is to evaluate the payment for observation stay versus readmission for patients who present to the emergency department.MethodsA retrospective review from 2014-2019 was conducted identifying all Medicare patients who had a primary, elective TJA and visited the ED within 90 days postoperatively. If a readmission was one midnight or less or had an equivalent diagnosis to an observation stay patient, it was characterized as a readmission that could have qualified as an observation stay. Using our institution’s average payment for Medicare readmissions and observations, actual and potential savings were calculated.ResultsSixty-nine out of 523 (13.2%) patients were placed under observation, while 454 (86.8%) patients were readmitted. Eighty-six out of 523 (18.9%) patients qualified for observation status. There was an actual savings of 11.8% by placing patients on observation status and readmission rate was decreased by 13.2%. Savings could have increased by a total of 27.7% and readmissions decreased by a total of 29.6% if all patients who qualified had been placed on observation status.ConclusionAt our institution, the implementation of observation stay has led to a savings of 11.8% and a potential total savings of 27.7%. The rate of readmissions was decreased by 13.2% and had the potential to decrease by a total of 29.6%. 相似文献
4.
Melinda L. Munang Catherine Browne Shaina Khanom Jason T. Evans E. Grace Smith Peter M. Hawkey Heinke Kunst Steven B. Welch Martin J. Dedicoat 《Emerging infectious diseases》2015,21(3):524-527
To determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in Birmingham, UK, during 2004–2013, we conducted enhanced epidemiologic investigation of molecular clusters. This technique identified exact locations of social mixing and chains of apparent recent transmission, which can be helpful for directing resources. 相似文献
5.
6.
Frequency,risk factors,and outcomes of central nervous system relapse in lymphoma patients treated with dose‐adjusted EPOCH plus rituximab
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7.
Yuan Xue Piotr Religa Renhai Cao Anker Jon Hansen Franco Lucchini Bernt Jones Yan Wu Zhenping Zhu Bronislaw Pytowski Yuxiang Liang Weide Zhong Paolo Vezzoni Bj?rn Rozell Yihai Cao 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(47):18513-18518
The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that “off-tumor” VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing neu. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs. 相似文献
8.
Estela M. Gierbolini-Norat Shaina D. Holman Peng Ding Shubham Bakshi Rebecca Z. German 《Dysphagia》2014,29(4):475-482
Feeding is a rhythmic behavior that consists of several component cycle types. How the timing of these cycles changes over a complete feeding sequence is not well known. To test the hypothesis that cycle frequency/duration changes as a function of time spent feeding, we examined complete feeding sequences in six infant pigs, using EMG of mylohyoid and thyrohyoid as cycle markers. We measured the instantaneous frequency of sucking and of swallowing cycles in 19 sequences. Each sequence contained three qualitatively distinctive phases of sucking frequency. Phase 1 started with cycles at a very high frequency and quickly dropped to a more constant level with low variation, which characterized phase 2. Phase 3 had a steady level of frequency but was interspersed with a number of high- or low-frequency cycles. Each phase differed from the others in patterns of within-phase variation and among-phase variation. Phase 2 had the least variation, and phase 3 had the largest range of frequencies. The number of sucks per swallow also differed among phases. These patterns, which characterize normative feeding, could indicate a physiologic basis in satiation. In human infant clinical studies, where data collection is often limited, these results indicated the utility of collecting data in different phases. Finally, these results can be used as a template or pattern with which to assess clinically compromised infants. 相似文献
9.
Xiaoshan Zhou Magnus Johansson Nicola Solaroli Björn Rozell Alf Grandien Anna Karlsson 《Journal of inherited metabolic disease》2010,33(3):231-236
Mitochondria are important for normal blood-cell development, and several diseases linked to mitochondrial DNA (mtDNA) show
hematological manifestations. We recently generated a mouse strain deficient in expression of the mitochondrial pyrimidine
nucleoside kinase thymidine kinase 2 (Tk2), showing that these mice exhibit progressive mtDNA depletion in multiple organs.
We used this mouse strain as a model for mtDNA depletion syndromes to investigate the effects of mtDNA depletion on hematopoiesis.
MtDNA levels in spleen from the Tk2-deficient mice were decreased 50%, but in contrast to all other investigated organs, both
thymus and peripheral blood leukocytes showed normal mtDNA levels. Analysis of peripheral blood and cell populations in spleen,
thymus, and bone marrow showed normal findings in the Tk2-deficient mice. The total rates of thymidine phosphorylation—which
also include phosphorylation catalyzed by cytosolic Tk 1—in both spleen and thymus from wild-type mice were >50-fold higher
than in liver, brain, and muscle. In summary, our data show that blood cells are less dependent on mitochondrial Tk2 compared
with several other tissues and that these cells can synthesize deoxyribonucleotides required for mtDNA replication by alternative
pathways such as phosphorylation of thymidine by cytosolic Tk1. 相似文献
10.
Fiaschi M Kolterud A Nilsson M Toftgård R Rozell B 《The American journal of pathology》2011,179(5):2569-2579
Hedgehog (Hh) signaling is a regulator of salivary gland morphogenesis, but its role in postnatal glands has only recently begun to be addressed. To examine the effects of deregulated Hh signaling in the salivary gland, we expressed the Hh effector protein GLI1, in salivary epithelial cells using both cytokeratin 5 and mouse mammary tumor virus (MMTV) transgenic systems. Ectopic pathway activation resulted in restrained acinar differentiation, formation of cystic lesions, and prominent appearance of ductal structures. Moreover, induced expression of GLI1 aids the formation of hyperplastic lesions, which closely resemble GLI1-induced changes in murine skin and mammary glands, suggesting that GLI1 targets cells with similar characteristics in different tissues. Furthermore, GLI1-expressing salivary epithelial cells are actively dividing, and GLI1-induced lesions are proliferative, an incident accompanied by enhanced expression of the Hh target genes, cyclin D1, and Snail. GLI1-induced salivary lesions regress after transgene withdrawal and become histologically normalized. Taken together, our data reveal the ability of GLI1 to modulate salivary acinar differentiation and to promote proliferation of ductal epithelial cells. 相似文献