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31.
Beltran J Matityahu A Hwang K Jbara M Maimon R Padron M Mota J Beltran L Sundaram M 《Skeletal radiology》2003,32(8):435-445
OBJECTIVE: To describe the normal MR anatomy and variations of the distal semimembranosus tendinous arms and the posterior oblique ligament as seen in the three orthogonal planes, to review the biomechanics of this complex and to illustrate pathologic examples. RESULTS AND CONCLUSION: The distal semimembranosus tendon divides into five tendinous arms named the anterior, direct, capsular, inferior and the oblique popliteal ligament. These arms intertwine with the branches of the posterior oblique ligament in the posterior medial aspect of the knee, providing stability. This tendon-ligamentous complex also acts synergistically with the popliteus muscle and actively pulls the posterior horn of the medial meniscus during knee flexion. Pathologic conditions involving this complex include complete and partial tears, insertional tendinosis, avulsion fractures and bursitis. 相似文献
32.
Rajagopalan S Olin JW Young S Erikson M Grossman PM Mendelsohn FO Regensteiner JG Hiatt WR Annex BH 《Human gene therapy》2004,15(6):619-624
The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial disease (PAD). VLTS-589 is an investigational nonviral therapeutic comprising a plasmid-expressing Del-1 formulated with poloxamer 188 (facilitating agent). One hundred subjects with bilateral PAD and IC will be randomized after careful screening to bilateral intramuscular delivery of VLTS-589 or placebo. A total of 84 mg of plasmid or placebo will be delivered as 42 intramuscular injections (2 ml per injection, 21 injections or 42 ml in each extremity of either plasmid or placebo) in both lower extremities. The subjects in the study will be followed at regular intervals for a year after study drug administration (days 30, 90, 180, and 365) with the primary endpoint being the safety and tolerability of VLTS-589 and change in peak walking time (PWT) at day 90. The secondary endpoints include percent and absolute change in resting ankle brachial Index, claudication onset time, and quality of life measured at various time points. DELTA-1 represents the largest plasmid-based gene transfer trial designed to test the efficacy of a Del-1 as a therapeutic approach in patients with IC caused by PAD. The novel aspects of the protocol include the usage of a Del-1 plasmid-polaxamer formulation to enhance gene transfer at doses that are an order of magnitude different than other comparable trials in a unique bilateral intramuscular dosing pattern to maximize transfection/clinical efficacy and general applicability to patients with PAD. 相似文献
33.
Andrzej Eljaszewicz Katarzyna Kleina Kamil Grubczak Urszula Radzikowska Paula Zembko Paulina Kaczmarczyk Marlena Tynecka Karolina Dworzanczyk Beata Naumnik Marcin Moniuszko 《Stem cell reviews》2018,14(5):686-693
IgA nephropathy (IgAN) is recognized as most frequent form of primary glomerulonephritis worldwide. IgAN is associated with renal degradation occurring due to irreversible pathological changes leading to glomerulosclerosis and interstitial fibrosis. It remains poorly understood whether and to what extent these changes are followed by the activation of regenerative mechanisms. Therefore, in this study we aimed to evaluate regenerative potential of IgAN patients by quantitating the frequencies of several stem cell types, namely circulating very small embryonic-like stem cells (VSELs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs) as well as different monocyte subsets with varying maturation and angiopoietic potential. Moreover, we analyzed whether changes in stem cell and monocyte frequencies were related to alterations of several chemotactic factors (stromal derived-factor (SDF-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)) and a marker of monocyte/macrophage activation, namely soluble form of CD163 receptor (sCD163). We showed that IgAN patients presented with enhanced levels of VSELs, but not other stem cell types. We also demonstrated significantly elevated numbers of intermediate monocytes known for their M2-like properties as well as high angiopoietic potential and CD163 expression. This finding was accompanied by detection of elevated sCD163 plasma levels in IgAN patients. Taking together, we demonstrated here that IgAN is associated with selective mobilization of VSELs and increased maturation of monocytes towards M2-like and angiopoietic phenotype. These findings contribute to better understanding of the role of regenerative mechanisms in the pathogenesis of chronic inflammation in the course of IgAN. 相似文献
34.
Matthew J. Gazzellone Mehdi Zarrei Christie L. Burton Susan Walker Mohammed Uddin S. M. Shaheen Julie Coste Rageen Rajendram Reva J. Schachter Marlena Colasanto Gregory L. Hanna David R. Rosenberg Noam Soreni Kate D. Fitzgerald Christian R. Marshall Janet A. Buchanan Daniele Merico Paul D. Arnold Stephen W. Scherer 《Journal of Neurodevelopmental Disorders》2016,8(1):36
Background
Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD.Methods
We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD.Results
We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p?=?1.85?×?10?03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4.Conclusions
Our findings suggest that rare CNVs may contribute to the etiology of OCD.35.
A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance 总被引:1,自引:0,他引:1
Samaddar JS Gaddy VT Duplantier J Thandavan SP Shah M Smith MJ Browning D Rawson J Smith SB Barrett JT Schoenlein PV 《Molecular cancer therapeutics》2008,7(9):2977-2987
This study identifies macroautophagy as a key mechanism of cell survival in estrogen receptor-positive (ER+) breast cancer cells undergoing treatment with 4-hydroxytamoxifen (4-OHT). This selective ER modifier is an active metabolite of tamoxifen commonly used for the treatment of breast cancer. Our study provides the following key findings: (a) only 20% to 25% of breast cancer cells treated with 4-OHT in vitro die via caspase-dependent cell death; more typically, the antiestrogen-treated ER+ breast cancer cells express increased levels of macroautophagy and are viable; (b) 4-OHT-induced cell death, but not 4-OHT-induced macroautophagy, can be blocked by the pan-caspase inhibitor z-VAD-fmk, providing strong evidence that these two outcomes of antiestrogen treatment are not linked in an obligatory manner; (c) 4-OHT-resistant cells selected from ER+ breast cancer cells show an increased ability to undergo antiestrogen-induced macroautophagy without induction of caspase-dependent cell death; and (d) 4-OHT, when used in combination with inhibitors of autophagosome function, induces robust, caspase-dependent apoptosis of ER+, 4-OHT-resistant breast cancer cells. To our knowledge, these studies provide the first evidence that macroautophagy plays a critical role in the development of antiestrogen resistance. We propose that targeting autophagosome function will improve the efficacy of hormonal treatment of ER+ breast cancer. 相似文献
36.
37.
38.
Elevated Blood Pressure in Urban Emergency Department Patients 总被引:1,自引:1,他引:0
David J. Karras MD Jacob W. Ufberg MD Katherine L. Heilpern MD John J. Cienki MD William K. Chiang MD Marlena M. Wald MPH Richard A. Harrigan MD David A. Wald DO Philip Shayne MD John Gaughan PhD Linda K. Kruus PhD 《Academic emergency medicine》2005,12(9):835-843
Objectives: There has been little systematic study of emergency department (ED) patients with elevated blood pressure (BP) values. The authors sought to characterize ED patients with elevated BP values, assess presenting symptoms, and determine the prevalence of elevated BP after discharge. Methods: This was a cross‐sectional study performed in four academic EDs. Adults presenting with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg were enrolled over a one‐week equivalent period. Demographics, medical history, and symptoms were obtained by chart abstraction and structured interview. A random patient subset underwent a three‐week follow‐up interview. BP measurements were staged, using Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC‐VI) criteria, according to the greatest value noted in the ED. Results: A total of 1,396 patients were enrolled. Stage 1 BP values were noted in 44.3%, stage 2 in 25.3%, and stage 3 in 30.3%. African American patients more frequently had stage 2 and 3 BP values than other ethnic groups. BP measurements were repeated in 61.1% of patients and were the same or greater in 51.3% of patients. Dyspnea was associated with greater BP values. Among the 63.9% of patients who were interviewed, 52.7% were not being treated for hypertension, and 42.1% of those with hypertension had recently missed a medication dose. Follow‐up was obtained in 74.7% of those targeted. A visit to a medical practitioner since discharge was reported by 63.2%; of these, 26.1% reported that their BP remained elevated. Conclusions: Elevated BP is common among ED patients. African American patients are more likely than those of other ethnic groups to have greater BP values. The ED visit may be a good opportunity to identify patients with unrecognized or poorly controlled hypertension. 相似文献
39.
Marek Pawlikowski Marlena Juszczak Ewa Karasek Barbara Muszyska Michal Karasek 《Journal of pineal research》1984,1(4):317-321
The effects of pinealectomy and of melatonin administration on prostaglandin E synthesis in the medial basal hypothalamus were studied in male rats. Melatonin treatment significantly decreased prostaglandin E release from the medial basal hypothalamus in pinealectomized rats. The results of the present study suggest that melatonin modulates hypothalamo-hypophyseal function, at least in part, via inhibition of hypothalamic prostaglandin synthesis. 相似文献
40.
Bernd Saugel Carolin Gramm Julia Y. Wagner Marlena Messer Tobias Lahmer Agnes S. Meidert Roland M. Schmid Wolfgang Huber 《Journal of critical care》2014