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Sample records for acute inferior mi

  1. Scorpion envenomation-induced acute thrombotic inferior myocardial infarction.

    PubMed

    Baykan, Ahmet Oytun; Gür, Mustafa; Acele, Armağan; Şeker, Taner; Çaylı, Murat

    2016-01-01

    The occurrence of a serious cardiac emergency following scorpion envenomation has rarely been reported and, when so, mostly presented as non-ST segment elevation myocardial infarction, cardiogenic shock, or myocarditis. Possible mechanisms include imbalance in blood pressure and coronary vasospasm caused by the combination of sympathetic excitation, scorpion venom-induced release of catecholamines, and the direct effect of the toxin on the myocardium. We report a case of a 55-year-old man who presented with acute inferior wall myocardial infarction (MI) within 2 h of being stung by a scorpion. Coronary angiogram revealed total thrombotic occlusion of the left circumflex artery, which was treated successfully with glycoprotein IIb/IIIa inhibitor, thrombus aspiration, antivenom serum, and supportive therapy. Therefore, life-threatening MI can complicate the clinical course during some types of scorpion envenomation and should be managed as an acute coronary syndrome. PMID:26875137

  2. Inferior phrenic artery pseudoaneurysm complicating drug-induced acute pancreatitis.

    PubMed

    Salem, Jean F; Haydar, Ali; Hallal, Ali

    2014-01-01

    Inferior phrenic artery (IPA) pseudoaneurysm is an extremely rare complication of chronic pancreatitis with only three cases reported in the literature so far. It is a serious condition that can be life-threatening if not diagnosed promptly. Recent advances in endovascular interventions made angiography with embolisation the modality of choice for diagnosis and treatment. We presented the first report of a case of ruptured IPA pseudoaneurysm complicating a drug-induced acute pancreatitis that was successfully treated by transcatheter arterial embolisation. Despite its rarity, rupture of pseudoaneurysm due to drug-induced pancreatitis should be suspected and included in the differential diagnosis when associated with haemodynamic instability. PMID:24385392

  3. [Acute inferior myocardial infarction after injection of etofenamate].

    PubMed

    Tekin, Yusuf Kenan; Tekin, Gülaçan

    2012-12-01

    Allergic symptoms accompanied by myocardial ischemic symptoms are defined as Kounis syndrome. Etofenamate is a safe and effective non-steroidal antiinflammatory drug that has widespread utilization. We hereby present a 71-year-old man with Kounis syndrome. Following intramuscular 1 g etofenamate injection, the clinical presentation when admitted to the emergency department (ED) was erythematous rash, pruritus, nausea and vomiting, dizziness, diaphoresis, and chest pain resulting in cardiopulmonary arrest. After 10 minutes of successful cardiopulmonary resuscitation, the electrocardiogram revealed acute inferior myocardial infarction. Patients who admit to the ED with allergic symptoms accompanied by chest pain should consider Kounis syndrome for prompt management. Electrocardiographic examination should be an essential part of the initial evaluation in such patients. PMID:23518891

  4. Adjunctive Inferior Vena Cava Filter Placement for Acute Pulmonary Embolism

    SciTech Connect

    Jha, V. M.; Lee-Llacer, J.; Williams, J.; Ubaissi, H.; Gutierrez, G.

    2010-08-15

    Inferior vena cava (IVC) filters are sometimes placed as an adjunct to full anticoagulation in patients with significant pulmonary embolism (PE). We aimed to determine the prevalence of adjunctive IVC filter placement in individuals diagnosed with PE, as well as the effect of adjunctive filter placement on mortality in patients with right heart strain associated with PE. This was a retrospective study of patients with acute PE treated with full anticoagulation admitted to a single academic medical center. Information abstracted from patient charts included presence or absence of right heart strain and of deep-vein thrombosis, and whether or not an IVC filter was placed. The endpoint was in-hospital mortality. Over 2.75 years, we found that 248 patients were diagnosed with acute PE, with an in-hospital mortality rate of 4.4%. The prevalence of adjunctive IVC filter placement was 13.3% (33 of 248), and the prevalence of documented right heart strain was 27.0% (67 of 248). In-hospital mortality was 10.2% in the non-filter-treated group (5 of 49), whereas there were no deaths in the filter-treated group (0 of 18); however, the difference was not statistically significant (P = 0.37). Both the presence of deep-vein thrombosis and of right heart strain increased the likelihood that an adjunctive IVC filter was placed (P < 0.0001 and P < 0.001, respectively). At our institution, patients were treated with IVC filters in addition to anticoagulation in 13.3% of cases of acute PE. Prospective studies or large clinical registries should be conducted to clarify whether this practice improves outcomes.

  5. Acute inferior homonymous quandrantanopia in a 71-year-old woman.

    PubMed

    Vachalová, Ivana; Gindl, Viola; Heckmann, Josef G

    2014-04-01

    A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex. PMID:24210803

  6. Difference between Outcome of Left Circumflex Artery and Right Coronary Artery Related Acute Inferior Wall Myocardial Infarction in Patients Undergoing Adjunctive Angioplasty after Fibrinolysis

    PubMed Central

    Sohrabi, Bahram; Separham, Ahmad; Madadi, Reza; Toufan, Mehrnoush; Mohammadi, Nasibeh; Aslanabadi, Naser; Kazemi, Babak

    2014-01-01

    Introduction: Prognostic differences between anterior and inferior wall Myocardial Infarction (MI) has been extensively investigated, but there is limited information about similar comparison between inferior wall MI caused by right coronary artery (RCA) and left circumflex artery (LCX) occlusion. The aim of present study was to compare prognostic differences between LCX- and RCA-related acute inferior wall ST-segment elevation MI (STEMI) treated by routine adjunctive angioplasty after receiving thrombolytic therapy (TLT). Methods: Between March 2012 and June 2013 one hundred fifty consecutive patients with acute inferior wall STEMI were studied. Patients were divided into two groups according to the infarct related artery (LCX vs. RCA). All patients underwent routine adjunctive angioplasty after TLT during the index hospitalization and clinical characteristics and outcomes were compared. Results: RCA and LCX arteries were occluded in 97 (64.7%) and 53 (35.3%) of patients, respectively. Two groups were similar in baseline characteristics except multiple-vessel disease was more prevalent with LCX occlusion (p= 0.008). There was a higher cardiac enzyme release (p< 0.001), more significant mitral regurgitation (MR) (p= 0.015), and lower left ventricular ejection fraction (LVEF) (p= 0.01) in patients with LCX occlusion. Multivariate analysis showed cTn-I release, occurrence of MR, and lower LVEF as independent factors leading to poor outcome. Conclusions: There were higher cTn-I release, MR occurrence, and lower LVEF in LCX-related acute inferior wall STEMI, all associated with poor outcome. Therefore, patients with ECG finding in favour of LCX occlusion should be considered as high risk and an invasive approach should be planned. PMID:25031825

  7. Haemodynamic collapse in a patient with acute inferior myocardial infarction and concomitant traumatic acute spinal cord injury.

    PubMed

    Kumagai, Naoto; Dohi, Kaoru; Tanigawa, Takashi; Ito, Masaaki

    2013-01-01

    A 71-year-old man suddenly collapsed and went into cardiopulmonary arrest. The cardiopulmonary resuscitation attempt succeeded in restoration of spontaneous circulation. The initial 12-lead electrocardiogram showed inferior acute myocardial infarction (AMI). The patient was initially diagnosed as having cardiogenic shock associated with inferior AMI. In spite of early coronary revascularisation, bradycardia and hypotension were sustained. After termination of sedation and extubation, he was found to have a quadriplegia and diagnosed with a cervical spinal cord injury (SCI). Therefore, the patient was finally diagnosed with neurogenic shock caused by acute cervical SCI due to the traumatic injury preceded by loss of consciousness complicating inferior AMI. We should recognise that SCI has unique haemodynamic features that mimic those associated with inferior AMI, but requires very different treatment. PMID:24272986

  8. miR expression profiling at diagnosis predicts relapse in pediatric precursor B-cell acute lymphoblastic leukemia.

    PubMed

    Avigad, Smadar; Verly, Iedan R N; Lebel, Asaf; Kordi, Oshrit; Shichrur, Keren; Ohali, Anat; Hameiri-Grossman, Michal; Kaspers, Gertjan J L; Cloos, Jacqueline; Fronkova, Eva; Trka, Jan; Luria, Drorit; Kodman, Yona; Mirsky, Hadar; Gaash, Dafna; Jeison, Marta; Avrahami, Galia; Elitzur, Sarah; Gilad, Gil; Stark, Batia; Yaniv, Isaac

    2016-04-01

    Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high-throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B-cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR-151-5p, and miR-451, and high expression of miR-1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5-fold increased risk of relapse (P = 0.041) in PCR-MRD non-high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5-fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non-BFM treated precursor B-cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR-151-5p, miR-451, and miR-1290 as a novel biomarker for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients. PMID:26684414

  9. The miRNA Plasma Signature in Response to Acute Aerobic Exercise and Endurance Training

    PubMed Central

    Nielsen, Søren; Åkerström, Thorbjörn; Rinnov, Anders; Yfanti, Christina; Scheele, Camilla; Pedersen, Bente K.; Laye, Matthew J.

    2014-01-01

    MiRNAs are potent intracellular posttranscriptional regulators and are also selectively secreted into the circulation in a cell-specific fashion. Global changes in miRNA expression in skeletal muscle in response to endurance exercise training have been reported. Therefore, our aim was to establish the miRNA signature in human plasma in response to acute exercise and chronic endurance training by utilizing a novel methodological approach. RNA was isolated from human plasma collected from young healthy men before and after an acute endurance exercise bout and following 12 weeks of endurance training. Global miRNA (742 miRNAs) measurements were performed as a screening to identify detectable miRNAs in plasma. Using customized qPCR panels we quantified the expression levels of miRNAs detected in the screening procedure (188 miRNAs). We demonstrate a dynamic regulation of circulating miRNA (ci-miRNA) levels following 0 hour (miR-106a, miR-221, miR-30b, miR-151-5p, let-7i, miR-146, miR-652 and miR-151-3p), 1 hour (miR-338-3p, miR-330-3p, miR-223, miR-139-5p and miR-143) and 3 hours (miR-1) after an acute exercise bout (P<0.00032). Where ci-miRNAs were all downregulated immediately after an acute exercise bout (0 hour) the 1 and 3 hour post exercise timepoints were followed by upregulations. In response to chronic training, we identified seven ci-miRNAs with decreased levels in plasma (miR-342-3p, let-7d, miR-766, miR-25, miR-148a, miR-185 and miR-21) and two miRNAs that were present at higher levels after the training period (miR-103 and miR-107) (P<0.00032). In conclusion, acute exercise and chronic endurance training, likely through specific mechanisms unique to each stimulus, robustly modify the miRNA signature of human plasma. PMID:24586268

  10. miR-146a and miR-155 Expression Levels in Acute Graft-Versus-Host Disease Incidence

    PubMed Central

    Atarod, Sadaf; Ahmed, Mohammed Mahid; Lendrem, Clare; Pearce, Kim Frances; Cope, Wei; Norden, Jean; Wang, Xiao-Nong; Collin, Matthew; Dickinson, Anne Mary

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for numerous hematological malignancies. However, acute graft-versus-host disease (aGVHD) is still the major complication causing mortality. MicroRNAs (miRNAs) play a significant role in inflammation and have potential as prognostic and diagnostic biomarkers. This study investigated the role of two immune-specific miRNAs (miR-146a and miR-155) as biomarkers for aGVHD incidence in the peripheral blood of allo-HSCT patients prior to disease onset. The study showed that miR-146a and its statistical interaction with miR-155 at day +28 were predictive of aGVHD incidence. Interestingly, the expression levels of miR-146a and miR-155 negatively correlated with the transcription factor, SPI1 (PU.1gene) mRNA expression. PMID:27014257

  11. Factors involved in the antinatriuretic effects of acute constriction of the thoracic and abdominal inferior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.

    1971-01-01

    Study of the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction in the absence of alterations in renal perfusion pressure. A comparison is made of the effects of equivalent degrees of TIVC and abdominal inferior vena cava constriction on arterial pressure, renal hemodynamics, and electrolyte excretion.

  12. Circulating miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in chronic heart failure patients

    PubMed Central

    Das, Saumya; Wang, Lemin; Jiang, Jinfa; Li, Guanghe; Xu, Jiahong; Yao, Jianhua; Wang, Hongbao; Dai, Yue; Xiao, Junjie

    2016-01-01

    Congestive heart failure (CHF) is a major cause of hospitalizations, morbidity, and mortality in Western societies. In addition to optimal medical and device therapy, exercise training is an important adjunct treatment option for CHF patients. MicroRNAs (miRNAs, miRs) participate in a variety of physiological and pathological processes. Dynamic regulation of circulating miRNAs during exercise in healthy persons and athletes has recently been documented, however, the response of circulating miRNAs to exercise in CHF patients is undetermined. Twenty-eight CHF patients underwent a symptom-limited incremental cardiopulmonary exercise test on a bicycle ergometer using a standardized exercise protocol of revised Ramp10 programs at Shanghai Tongji Hospital. Blood samples were collected before and immediately after an acute exercise session. RNA was extracted from the serum and selected miRNAs were determined using quantitative polymerase chain reactions. Moreover, inflammatory and muscle damage markers were determined by enzyme linked immunosorbent assays. We found that serum miR-21, miR-378 and miR-940 levels were significantly up-regulated immediately following an acute exercise while the rest were not changed. In addition, no robust correlation was identified between changes of these miRNAs and exercise capacity, muscle damage or inflammation. In conclusion, serum miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in CHF patients. Further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of exercise adaptation in CHF patients, and if they have any use as prognostic markers of cardiovascular outcomes. PMID:26799589

  13. Acute wiiitis representing as thrombosis of the inferior vena cava and left pelvic veins.

    PubMed

    Brodmann, M; Gary, T; Hafner, F; Eller, P; Deutschmann, H; Pilger, E; Seinost, G

    2015-08-01

    Deep venous thrombosis as a result of venous wall injury provoked by trauma is a common finding. It often occurs in patients with sportive overstraining, caused by over fatigue of the body structures. In 2007, the entity of "acute wiiitis" was first described in a letter to the New England Journal of Medicine. Acute wiiitis sums up all affections, mainly skeletal and muscle affections, provoked by playing Nintendo Wii, a very common and loved video-game system. Deep venous thrombosis as a consequence of Nintendo Wii has not been described so far. We present a patient with a massive free floating thrombus of the left pelvic veins originating from the gluteal veins and reaching into the inferior vena cava after playing Nintendo Wii. PMID:24681523

  14. Serum miRNA-499 and miRNA-210: A potential role in early diagnosis of acute coronary syndrome.

    PubMed

    Shalaby, Sally M; El-Shal, Amal S; Shoukry, Amira; Khedr, Mohamad H; Abdelraheim, Nader

    2016-08-01

    In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. © 2016 IUBMB Life, 68(8):673-682, 2016. PMID:27346801

  15. Differentially expressed miRNAs in acute wound healing of the skin: a pilot study.

    PubMed

    Li, Ping; He, Quanyong; Luo, Chengqun; Qian, Liyuan

    2015-02-01

    The aim of the present study was to compare expression of microRNAs (miRNAs) from scar and normal skin areas in patients who suffered acute injuries in the skin. A total of 9 patients with acute injuries in the skin who received surgical treatment from December 2012 to March 2013 were included in this pilot study. Specimens from the hypertrophic scar and normal skin areas were obtained from the same patient during surgery. To screen for differentially expressed miRNAs, we applied 3 statistical methods, namely the traditional t test, the false discovery rate (FDR), and a novel sure independence screening procedure based on the distance correlation (DC-SIS). We examined the functional trends and metabolic and regulatory pathways for the target genes of the identified miRNAs, and explored interaction of these miRNAs in the implication of scar healing using Ingenuity Pathway Analysis. DC-SIS identified 18 differentially expressed miRNAs, 4 of which (miR-149, miR-203a, miR-222, miR-122) were also identified by FDR. The target genes of the 4 miRNAs exhibit a variety of biological functions, and are involved in various pathways such as mitogen-activated protein kinase, Wnt signaling, and focal adhesion. We identified 1 network in which 14 out of the 18 differentially expressed miRNAs were involved. Many of the miRNAs in the network target genes were involved in cell proliferation and apoptosis.In this pilot study, we identified several miRNAs exhibiting differential expression in patients who suffered acute injuries in the skin. Further studies on these miRNAs are needed to validate our findings and explore their roles in the wound healing process of the skin. PMID:25700309

  16. Circulating miR-499 as a potential biomarker for acute myocardial infarction

    PubMed Central

    Xin, Yunyi

    2016-01-01

    Acute myocardial infarction (AMI), a common heart disease that may lead to chronic heart failure, is the leading cause of morbidity and mortality worldwide. MicroRNAs (miRNAs) are small non-coding RNAs that mediate the expression of target genes. Recently, a number of miRNAs are emerging as potential biomarkers of AMI. MiRNA-499 is a newly discovered member of miRNAs, and is mainly expressed in myocardium, the circulating levels of miRNA-499 was increased in AMI patients. This review summarizes the latest advances in the miRNA-499 study and discusses the potential of miRNA-499 to be a biomarker of AMI. PMID:27162785

  17. Circulating miR-499 as a potential biomarker for acute myocardial infarction.

    PubMed

    Xin, Yunyi; Yang, Chengjian; Han, Zhijun

    2016-04-01

    Acute myocardial infarction (AMI), a common heart disease that may lead to chronic heart failure, is the leading cause of morbidity and mortality worldwide. MicroRNAs (miRNAs) are small non-coding RNAs that mediate the expression of target genes. Recently, a number of miRNAs are emerging as potential biomarkers of AMI. MiRNA-499 is a newly discovered member of miRNAs, and is mainly expressed in myocardium, the circulating levels of miRNA-499 was increased in AMI patients. This review summarizes the latest advances in the miRNA-499 study and discusses the potential of miRNA-499 to be a biomarker of AMI. PMID:27162785

  18. Precordial ST segment depression during acute inferior myocardial infarction: early thallium-201 scintigraphic evidence of adjacent posterolateral or inferoseptal involvement

    SciTech Connect

    Lew, A.S.; Weiss, A.T.; Shah, P.K.; Maddahi, J.; Peter, T.; Ganz, W.; Swan, H.J.; Berman, D.S.

    1985-02-01

    To investigate the myocardial perfusion correlates of precordial ST segment depression during acute inferior myocardial infarction, a rest thallium-201 scintigram and a closely timed 12 lead electrocardiogram were obtained within 6 hours of the onset of infarction in 44 patients admitted with their first acute inferior myocardial infarction. Thirty-six patients demonstrated precordial ST segment depression (group 1) and eight did not (group 2). A perfusion defect involving the inferior wall was present in all 44 patients. Additional perfusion defects of the adjacent posterolateral wall (n . 20), the ventricular septum (n . 9) or both (n . 6) were present in 35 of 36 patients from group 1 compared with only 1 of 8 patients from group 2 (p less than 0.001). There was no significant difference in the frequency of multivessel coronary artery disease or disease of the left anterior descending artery between group 1 and group 2 or between patients with and those without a thallium-201 perfusion defect involving the ventricular septum. Thus, precordial ST segment depression during an acute inferior myocardial infarction is associated with thallium-201 scintigraphic evidence of more extensive involvement of the adjacent posterolateral or inferoseptal myocardial segments, which probably reflects the extent and pattern of distribution of the artery of infarction, rather than the presence of coexistent multivessel coronary artery disease or disease of the left anterior descending artery.

  19. New approach of assessing hypovolemic shock class 1 during acute emergencies: Ultrasonographic inferior vena cava and abdominal aorta diameter ratio

    NASA Astrophysics Data System (ADS)

    Ahmad, Rashidi; Kunji, Mohamad Iqhbal; Hj Abd Kareem, Meera Mohaideen; Halim, Shamimi A.

    2013-09-01

    In a patient with hypovolemic shock class 1, the vital signs and biochemical properties are almost normal. The alteration of hemodynamic parameters and biochemical values occurs mainly in advanced hypovolemia state (neuroendocrine response). The availability of ultrasound machine at healthcare centers makes the measurement of vascular calibre feasible and possible. Inspiration and expiration inferior vena cava diameter changes predict hypovolemic shock class 1 but in acute emergencies this method is impractical. The purpose of this study is to develop a new approach in identifying hypovolemic shock at early phase by measuring the inferior vena cava and aorta diameter ratio using bedside ultrasound machine.

  20. Successful Treatment of Acute on Chronic Mesenteric Ischaemia by Common Iliac to Inferior Mesenteric Artery Bypass

    PubMed Central

    Coakley, D. N.; Shaikh, F. M.; Kavanagh, E. G.

    2015-01-01

    Chronic mesenteric ischaemia is a rare and potentially fatal condition most commonly due to atherosclerotic stenosis or occlusion of two or more mesenteric arteries. Multivessel revascularisation of both primary mesenteric vessels, the celiac artery and superior mesenteric artery (SMA), is the current mainstay of treatment; however, in a certain cohort of patients, revascularisation one or both vessels may not be possible. Arteries may be technically unreconstructable or the patient may be surgically unfit for the prolonged aortic cross clamping times required. Here we present a case involving a 72-year-old woman with acute on chronic mesenteric ischaemia. She was a high risk surgical patient with severe unreconstructable stenotic disease of the SMA and celiac arteries. She was successfully treated with single vessel revascularisation of the inferior mesenteric artery (IMA) via a common iliac to IMA reversed vein bypass. At two-year follow-up, the graft remains patent and the patient continues to be symptom-free and is maintaining her weight. PMID:26421207

  1. Inferior ST-Elevation Acute Myocardial Infarction or an Inferior-Lead Brugada-like Electrocardiogram Pattern Associated With the Use of Pregabalin and Quetiapine?

    PubMed

    Brunetti, Natale D; Ieva, Riccardo; Correale, Michele; Cuculo, Andrea; Santoro, Francesco; Guaricci, Andrea I; De Gennaro, Luisa; Gaglione, Antonio; Di Biase, Matteo

    2016-01-01

    The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation (>2 mm) in the right precordial leads. We report the case of a 62-year-old man, with bipolar disorder, admitted to the emergency department because of dyspnea and chest discomfort. The patient was on treatment with pregabalin and quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST-elevation, more evident in inferior leads, where a Brugada-like pattern was present. The patient underwent coronary angiography with a diagnosis of suspected acute coronary syndrome. Coronary angiography, however, showed mild coronary artery disease not requiring coronary angioplasty. Echocardiography did not reveal left ventricular dysfunction or pericardial effusion. Troponin levels remained normal over serial controls. Eventually, chest radiography showed lung opacities and consolidation suggestive for pneumonia. To the best of our knowledge, this is one of the first cases showing a transient Brugada-like electrocardiogram pattern in inferior leads, probably amplified by the administration of pregabalin and quetiapine. PMID:26291591

  2. Right coronary artery dissection and aneurysm presented as acute inferior myocardial infarction from an automobile airbag trauma.

    PubMed

    Zeng, Chunlai; Hu, Wuming; Zhu, Ning; Zhao, Xuyong; Xu, Jian; Ye, Shiyong; Xiang, Yijia; Lv, Linchun

    2015-10-01

    Coronary artery dissection and aneurysm culminating in acute myocardial infarction are rare after blunt chest trauma. We are reporting a case of a previously healthy 52-year-old man who presented with right inferior lobe contusion, pleural effusion, right interlobar fissure effusion, bone fracture of right fourth rib, and acute inferior wall myocardial infarction and who experienced blunt trauma in his right chest wall by an airbag deployment in a car accident. Coronary angiography showed an aneurysm in the middle of right coronary artery with 70% afferent narrowing just distal to the aneurysm with no visible atherosclerotic lesion. A 4.0×20 mm TEXUS Liberté stent in the lesion was deployed, and a good coronary flow was obtained without residual stenosis and the aneurysm vanished. PMID:26319191

  3. Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

    PubMed Central

    Xiong, Qian; Yang, Yadong; Wang, Hai; Li, Jie; Wang, Shaobin; Li, Yanming; Yang, Yaran; Cai, Kan; Ruan, Xiuyan; Yan, Jiangwei; Hu, Songnian; Fang, Xiangdong

    2014-01-01

    Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias. PMID:24755403

  4. Global miRNA expression is temporally correlated with acute kidney injury in mice

    PubMed Central

    Chen, Xiao

    2016-01-01

    MicroRNAs (miRNAs) are negative regulators of gene expression and protein abundance. Current evidence shows an association of miRNAs with acute kidney injury (AKI) leading to substantially increased morbidity and mortality. Here, we investigated whether miRNAs are inductive regulators responsible for the pathological development of AKI. Microarray analysis was used to detect temporal changes in global miRNA expression within 48 h after AKI in mice. Results indicated that global miRNA expression gradually increased over 24 h from ischemia reperfusion injury after 24 h, and then decreased from 24 h to 48 h. A similar trend was observed for the index of tubulointerstitial injury and the level of serum creatinine, and there was a significant correlation between the level of total miRNA expression and the level of serum creatinine (p < 0.05). This expression-phenotype correlation was validated by quantitative reverse transcription PCR on individual miRNAs, including miR-18a, -134, -182, -210 and -214. Increased global miRNA expression may lead to widespread translational repression and reduced cellular activity. Furthermore, significant inflammatory cytokine release and peritubular capillary loss were observed, suggesting that the initiation of systematic destruction programs was due to AKI. Our findings provide new understanding of the dominant role of miRNAs in promoting the pathological development of AKI. PMID:26966664

  5. Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon

    PubMed Central

    Ramsingh, Giridharan; Jacoby, Meagan A.; Shao, Jin; De Jesus Pizzaro, Rigoberto E.; Shen, Dong; Trissal, Maria; Getz, Angela H.; Ley, Timothy J.; Walter, Matthew J.

    2013-01-01

    Altered microRNA (miRNA) expression is frequently observed in acute myelogenous leukemia (AML) and has been implicated in leukemic transformation. Whether somatic copy number alterations (CNAs) are a frequent cause of altered miRNA gene expression is largely unknown. Herein, we used comparative genomic hybridization with a custom high-resolution miRNA-centric array and/or whole-genome sequence data to identify somatic CNAs involving miRNA genes in 113 cases of AML, including 50 cases of de novo AML, 18 cases of relapsed AML, 15 cases of secondary AML following myelodysplastic syndrome, and 30 cases of therapy-related AML. We identified a total of 48 somatic miRNA gene-containing CNAs that were not identified by routine cytogenetics in 20 patients (18%). All these CNAs also included one or more protein coding genes. We identified a single case with a hemizygous deletion of MIR223, resulting in the complete loss of miR-223 expression. Three other cases of AML were identified with very low to absent miR-223 expression, an miRNA gene known to play a key role in myelopoiesis. However, in these cases, no somatic genetic alteration of MIR223 was identified, suggesting epigenetic silencing. These data show that somatic CNAs specifically targeting miRNA genes are uncommon in AML. PMID:24009227

  6. Anterior ST depression with acute transmural inferior infarction due to posterior infarction. A vectorcardiographic and scintigraphic study

    SciTech Connect

    Mukharji, J.; Murray, S.; Lewis, S.E.; Croft, C.H.; Corbett, J.R.; Willerson, J.T.; Rude, R.E.

    1984-07-01

    The hypothesis that anterior ST segment depression represents concomitant posterior infarction was tested in 49 patients admitted with a first transmural inferior myocardial infarction. Anterior ST depression was defined as 0.1 mV or more ST depression in leads V1, V2 or V3 on an electrocardiogram recorded within 18 hours of infarction. Serial vectorcardiograms and technetium pyrophosphate scans were obtained. Eighty percent of the patients (39 of 49) had anterior ST depression. Of these 39 patients, 34% fulfilled vectorcardiographic criteria for posterior infarction, and 60% had pyrophosphate scanning evidence of posterior infarction. Early anterior ST depression was neither highly sensitive (84%) nor specific (20%) for the detection of posterior infarction as defined by pyrophosphate imaging. Of patients with persistent anterior ST depression (greater than 72 hours), 87% had posterior infarction detected by pyrophosphate scan. In patients with inferior myocardial infarction, vectorcardiographic evidence of posterior infarction correlated poorly with pyrophosphate imaging data. Right ventricular infarction was present on pyrophosphate imaging in 40% of patients with pyrophosphate changes of posterior infarction but without vectorcardiographic evidence of posterior infarction. It is concluded that: 1) the majority of patients with acute inferior myocardial infarction have anterior ST segment depression; 2) early anterior ST segment depression in such patients is not a specific marker for posterior infarction; and 3) standard vectorcardiographic criteria for transmural posterior infarction may be inaccurate in patients with concomitant transmural inferior myocardial infarction or right ventricular infarction, or both.

  7. The 5’ flanking region of miR-378 is hypomethylated in acute myeloid leukemia

    PubMed Central

    Zhu, Xiao-Wen; Wen, Xiang-Mei; Zhang, Ying-Ying; Yang, Lei; Guo, Hong; Yang, Jing; Zhang, Ming; Yin, Jia-Yu; Ma, Ji-Chun; Lin, Jiang; Deng, Zhao-Qun; Qian, Jun

    2015-01-01

    Background: Aberrant expression of miR-378 has been observed in various malignancies including acute myeloid leukemia (AML). However, the mechanism regulating of miR-378 expression remains unknown. This study was aimed to investigate miR-378 methylation and to explore its clinical significance in AML. Methods: Methylation status of miR-378 5’-flanking region was investigated by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite-sequencing PCR (BSP). The expression of miR-378 was evaluated by real-time quantitative PCR (RQ-PCR). The correlation between expression of miR-378 and 5’-flanking region methylation was analyzed using 5-aza-2’-deoxycytidine (5-aza-dC) treatment. Results: miR-378 5’-flanking region was significantly hypomethylated in AML patients compared to controls (median 0.109 vs. 0.058) (P=0.048). miR-378 expression was correlated with miR-378 5’-flanking region in leukemic cell line treated with 5-aza-dC, but not in AML patients. The level of miR-378 hypomethylation significantly increased in M2 subtype compared to other subtypes. Moreover, patients with t(8;21) harbored the highest level of miR-378 hypomethylation. However, there was no significant difference in overall survival between patients with high and low miR-378 hypomethylation. The association of miR-378 expression with methylation was not observed in AML patients, but miR-378 expression in THP-1 line was increased while methylation status of miR-378 5-flanking region was decreased after 5-aza-dC treatment. Conclusions: Our findings suggest that miR-378 is reactivated by demethylation after 5-aza-dC treatment. 5’-flanking region of miR-378 is hypomethylated in AML especially in those with t(8;21). PMID:26191124

  8. Enforced expression of miR-125b attenuates LPS-induced acute lung injury.

    PubMed

    Guo, Zhongliang; Gu, Yutong; Wang, Chunhong; Zhang, Jie; Shan, Shan; Gu, Xia; Wang, Kailing; Han, Yang; Ren, Tao

    2014-11-01

    The acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Recent evidence implicated a potential role of miR-125b in development of ALI. Here we evaluated the miR-125b-based strategy in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We found that up-regulation of miR-125b expression maintained the body weight and survival of ALI mice, and significantly reduced LPS-induced pulmonary inflammation as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Further, enforced expression of miR-125b resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin and IgM in BAL fluid, and ameliorated the histopathology changes of lung in LPS-induced ALI mice. Of interest, serum miR-125b expression was also decreased and inversely correlated with the disease severity in patients with ARDS. Our findings strongly demonstrated that enforced expression of miR-125b could effectively ameliorate the LPS-induced ALI, suggesting a potential application for miR-125b-based therapy to treat clinical ARDS. PMID:25004393

  9. MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status

    PubMed Central

    2012-01-01

    Background MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. Findings We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD) with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status. Conclusions This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively. PMID:22681934

  10. Acute Kidney Injury Associated with Renal Cell Carcinoma Complicated by Renal Vein and Inferior Vena Cava Involvement.

    PubMed

    Sugase, Taro; Akimoto, Tetsu; Kubo, Taro; Imai, Toshimi; Otani-Takei, Naoko; Miki, Takuya; Takeda, Shin-Ichi; Nukui, Akinori; Muto, Shigeaki; Morita, Tatsuo; Nagata, Daisuke

    2016-01-01

    Acute kidney injury (AKI) is caused by diverse pathologies, although it may occasionally result from concurrent renal efflux disturbances. We herein describe a case of AKI in a patient complicated by renal cell carcinoma (RCC) with renal vein and inferior vena cava (IVC) involvement. A neoplastic thrombus which disrupted the blood flow in the renal vein appeared to play a role in the rapid decline in the renal function. Such a scenario has rarely been mentioned in the previous literature describing the cases of RCC complicated by AKI. Concerns regarding the diagnostic and therapeutic strategies for RCC are also discussed. PMID:27580548

  11. Diagnostic value of miR-30d-5p and miR-125b-5p in acute myocardial infarction

    PubMed Central

    JIA, KEGANG; SHI, PING; HAN, XUEJING; CHEN, TIENAN; TANG, HONGXIA; WANG, JING

    2016-01-01

    Rapid and accurate differential diagnosis of acute myocardial infarction (AMI) is crucial for timely interventions and the improvement of prognosis. However, this is difficult to achieve using current methods. Therefore, the present study aimed to evaluate the suitability of circulating microRNAs (miRNAs) as AMI biomarkers in patients with acute coronary syndrome (ACS). miRNA profiling in plasma samples from patients with AMI (n=3) and healthy controls (n=3) was performed using microarrays. Results were then validated in five patients and five healthy controls. miRNA-125b-5p and miR-30d-5p expression levels were quantified in plasma samples from 230 patients with ACS and 79 healthy controls using reverse transcription-quantitative polymerase chain reaction. Routine diagnostic parameters were assessed, including creatinine kinase MB, cardiac troponin I (cTnI) and myoglobin. A total of 33 miRNAs were differentially expressed in patients with AMI and healthy controls. Following validation based on the previously established roles for these miRNAs, six miRNAs were validated. miR-125b-5p and miR-30d-5p were selected for further investigation. Expression levels of miR-125b-5p and miR-30d-5p in plasma were higher in patients with ACS compared with the healthy controls (P<0.001). Receiver operating characteristic curve analysis revealed that the area under the curve of miR-30d-5p was higher than that of cTnI (0.915 and 0.899). miR-125b-5p (sensitivity, 0.808; specificity, 0.845) and miR-30d-5p (sensitivity, 0.855; specificity, 0.810) were suitable diagnostic predictors of AMI. Kaplan-Meier survival analysis indicated that miR-125b-5p levels were associated with 6 month cardiovascular events in patients with AMI, but not miR-30d-5p. miR-125b-5p and miR-30d-5p presented a diagnostic value for early diagnosis of AMI, and miR-30d-5p may have a higher diagnostic value than cTnI. PMID:27176713

  12. Diagnostic value of miR-30d-5p and miR-125b-5p in acute myocardial infarction.

    PubMed

    Jia, Kegang; Shi, Ping; Han, Xuejing; Chen, Tienan; Tang, Hongxia; Wang, Jing

    2016-07-01

    Rapid and accurate differential diagnosis of acute myocardial infarction (AMI) is crucial for timely interventions and the improvement of prognosis. However, this is difficult to achieve using current methods. Therefore, the present study aimed to evaluate the suitability of circulating microRNAs (miRNAs) as AMI biomarkers in patients with acute coronary syndrome (ACS). miRNA profiling in plasma samples from patients with AMI (n=3) and healthy controls (n=3) was performed using microarrays. Results were then validated in five patients and five healthy controls. miRNA-125b-5p and miR-30d-5p expression levels were quantified in plasma samples from 230 patients with ACS and 79 healthy controls using reverse transcription-quantitative polymerase chain reaction. Routine diagnostic parameters were assessed, including creatinine kinase MB, cardiac troponin I (cTnI) and myoglobin. A total of 33 miRNAs were differentially expressed in patients with AMI and healthy controls. Following validation based on the previously established roles for these miRNAs, six miRNAs were validated. miR‑125b‑5p and miR‑30d‑5p were selected for further investigation. Expression levels of miR‑125b‑5p and miR‑30d‑5p in plasma were higher in patients with ACS compared with the healthy controls (P<0.001). Receiver operating characteristic curve analysis revealed that the area under the curve of miR‑30d‑5p was higher than that of cTnI (0.915 and 0.899). miR‑125b‑5p (sensitivity, 0.808; specificity, 0.845) and miR‑30d‑5p (sensitivity, 0.855; specificity, 0.810) were suitable diagnostic predictors of AMI. Kaplan-Meier survival analysis indicated that miR-125b-5p levels were associated with 6 month cardiovascular events in patients with AMI, but not miR‑30d‑5p. miR-125b-5p and miR-30d-5p presented a diagnostic value for early diagnosis of AMI, and miR‑30d‑5p may have a higher diagnostic value than cTnI. PMID:27176713

  13. Acute Traumatic Renal Artery to Inferior Vena Cava Fistula Treated with a Covered Stent

    SciTech Connect

    Tam, J.; Kossman, T.; Lyon, S.

    2006-12-15

    A 34-year-old man presented within hours of suffering a penetrating stab wound and was diagnosed with a right renal artery to inferior vena cava fistula. Initial attempts at excluding the fistula with a balloon were unsuccessful. He was subsequently treated with a covered stent inserted into the right renal artery which successfully excluded the fistula.

  14. Delineation of QRS offset by instantaneous changes in ECG vector angle can improve detection of acute inferior myocardial infarctions.

    PubMed

    Starc, Vito; Schlegel, Todd T

    2016-01-01

    We developed an automated new method for determining QRS offset, based on angular velocity (AV) changes around the QRS loop, and compared the method's performance to that of manual and more established automated methods for determining QRS offset in both healthy subjects and patients with acute myocardial infarction (AMI). Specifically, using Frank leads reconstructed from standard 12-lead ECGs, we determined AV in the direction of change raised to the 4th power, d(t). We found that the d(t)-determined AV transition (ΔAV) nearly coincided with manually determined QRS offset in healthy subjects, and in 27 patients with anterior AMI. However, in 31 patients with inferior AMI, ΔAV typically preceded that of QRS offset determined by the established automated methods, and by more than 10ms in 32% of cases. While this "ΔAV precedence" coincided with diagnostic ST elevation in only a minority of patients with recent inferior AMI, the use of ΔAV precedence as a complement to traditional determination of ST elevation increased the sensitivity for detecting inferior AMIs from 23 to 42%. PMID:26979381

  15. Acute cervical artery dissection after a dental procedure due to a second inferior molar infection.

    PubMed

    Delgado, Montserrat G; Riesco, Nuria; Murias, Eduardo; Calleja, Sergio

    2015-01-01

    Periodontal infections might represent one of the causative factors for cervical artery dissection. We present a case of a 49-year-old woman admitted due to headache. The patient had been suffering from a right second inferior molar infection with a cervical phlegmon for 1 week prior to admission. On 2 October 2014, the patient went to the dentist and a molar extraction was performed in the morning. In the afternoon, the patient began to experience right hemifacial pain that progressed towards an intense and bilateral headache. Neurological status at the time of admission revealed right miosis, ptosis and conjuntival hyperaemia. A CT angiography showed a right internal carotid artery dissection provoking a high-degree stenosis. The relationship between periodontal infection and vascular disease has been previously presented. Microbial agents may directly, and inflammatory and immunological host response indirectly, influence inflammatory changes in cervical arteries favouring dissections with minor traumas. PMID:26038385

  16. Circulating miR-221-3p as a novel marker for early prediction of acute myocardial infarction.

    PubMed

    Coskunpinar, Ender; Cakmak, Huseyin Altug; Kalkan, Ali Kemal; Tiryakioglu, Necip Ozan; Erturk, Mehmet; Ongen, Zeki

    2016-10-10

    Recent studies have reported circulating microRNAs (miRNAs) as novel biomarkers for cardiovascular diseases including acute myocardial infarction, heart failure, diabetes mellitus, stroke, and acute pulmonary embolism. The aims of this study were 1) to compare the plasma expression levels of miRNAs in patients with acute coronary syndrome (ACS) and control subjects and in ST-elevation myocardial infarction (STEMI) and non-STEMI 2) to evaluate miRNAs potential to be used as novel diagnostic biomarkers for ACS. Twenty seven consecutive patients, admitted to emergency department of a training and research hospital between January-December 2013 with acute chest pain and/or dyspnea and diagnosed with ACS, and 16 non-ACS control subjects were included in this study. miRNA profiling was performed by using real time polymerase chain reaction. Functions of dysregulated miRNAs were evaluated by computerized-pathways analysis. miR-221-3p was one of the two most dysregulated miRNAs with a fold regulation of 3.89. It was significantly positively correlated with both Troponin and GRACE and Synthax Score. Moreover, miR221-3p was found to be significantly inversely correlated with left ventricular ejection fraction. miR-221-3p was the most prominent biomarker candidate with an area under curve (AUC) level of 0.881 (95% confidence interval: 0.774-0.987; p=0.002). The present study is the first to report an increased expression levels of miR-221-3p in AMI. Since miR-221-3p has a high discriminative value and significant relations with Troponin, GRACE and Synthax score and left ventricular systolic function, it may be a potential biomarker for early prediction of AMI. PMID:27374153

  17. Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia

    PubMed Central

    Mi, Shuangli; Li, Zejuan; Chen, Ping; He, Chunjiang; Cao, Donglin; Elkahloun, Abdel; Lu, Jun; Pelloso, Luis A.; Wunderlich, Mark; Huang, Hao; Luo, Roger T.; Sun, Miao; He, Miao; Neilly, Mary Beth; Zeleznik-Le, Nancy J.; Thirman, Michael J.; Mulloy, James C.; Liu, Paul P.; Rowley, Janet D.; Chen, Jianjun

    2010-01-01

    MicroRNA (miRNA)-17-92 cluster (miR-17-92), containing seven individual miRNAs, is frequently amplified and overexpressed in lymphomas and various solid tumors. We have found that it is also frequently amplified and the miRNAs are aberrantly overexpressed in mixed lineage leukemia (MLL)-rearranged acute leukemias. Furthermore, we show that MLL fusions exhibit a much stronger direct binding to the locus of this miRNA cluster than does wild-type MLL; these changes are associated with elevated levels of histone H3 acetylation and H3K4 trimethylation and an up-regulation of these miRNAs. We further observe that forced expression of this miRNA cluster increases proliferation and inhibits apoptosis of human cells. More importantly, we show that this miRNA cluster can significantly increase colony-forming capacity of normal mouse bone marrow progenitor cells alone and, particularly, in cooperation with MLL fusions. Finally, through combinatorial analysis of miRNA and mRNA arrays of mouse bone marrow progenitor cells transfected with this miRNA cluster and/or MLL fusion gene, we identified 363 potential miR-17-92 target genes that exhibited a significant inverse correlation of expression with the miRNAs. Remarkably, these potential target genes are significantly enriched (P < 0.01; >2-fold) in cell differentiation, hematopoiesis, cell cycle, and apoptosis. Taken together, our studies suggest that overexpression of miR-17-92 cluster in MLL-rearranged leukemias is likely attributed to both DNA copy number amplification and direct up-regulation by MLL fusions, and that the miRNAs in this cluster may play an essential role in the development of MLL-associated leukemias through inhibiting cell differentiation and apoptosis, while promoting cell proliferation, by regulating relevant target genes. PMID:20133587

  18. Increased expression of miR-24 is associated with acute myeloid leukemia with t(8;21).

    PubMed

    Yin, Jia-Yu; Tang, Qin; Qian, Wei; Qian, Jun; Lin, Jiang; Wen, Xiang-Mei; Zhou, Jing-Dong; Zhang, Ying-Ying; Zhu, Xiao-Wen; Deng, Zhao-Qun

    2014-01-01

    This study was designed to learn the expression status of miR-24 and its clinical relevance in patients with acute myeloid leukemia (AML). We detected the miR-24 expression levels using real-time quantitative PCR in 84 AML patients and investigated the clinical significance of miR-24 expression in AML. There was no difference in clinical parameters between cases with miR-24 high expression and with miR-24 low expression. The frequency of miR-24 high expression was higher in patients with t(8;21) than in others (82% (9/11) versus 44% (32/72), P=0.026). The levels of miR-24 expression had no correlation with the mutations of nine genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). Meanwhile, among the group who obtained CR, the cases with miR-24 high expression had no difference in overall survival (OS) and relapse-free survival (RFS) than those with miR-24 low expression (P=0.612 and 0.665, respectively). These findings implicated that miR-24 high regulation is a common event in AML with t(8;21), and it might serve as a novel and selective therapeutic target for the treatment of AML with t(8;21). PMID:25550847

  19. Increased expression of miR-24 is associated with acute myeloid leukemia with t(8;21)

    PubMed Central

    Yin, Jia-Yu; Tang, Qin; Qian, Wei; Qian, Jun; Lin, Jiang; Wen, Xiang-Mei; Zhou, Jing-Dong; Zhang, Ying-Ying; Zhu, Xiao-Wen; Deng, Zhao-Qun

    2014-01-01

    This study was designed to learn the expression status of miR-24 and its clinical relevance in patients with acute myeloid leukemia (AML). We detected the miR-24 expression levels using real-time quantitative PCR in 84 AML patients and investigated the clinical significance of miR-24 expression in AML. There was no difference in clinical parameters between cases with miR-24 high expression and with miR-24 low expression. The frequency of miR-24 high expression was higher in patients with t(8;21) than in others (82% (9/11) versus 44% (32/72), P=0.026). The levels of miR-24 expression had no correlation with the mutations of nine genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). Meanwhile, among the group who obtained CR, the cases with miR-24 high expression had no difference in overall survival (OS) and relapse-free survival (RFS) than those with miR-24 low expression (P=0.612 and 0.665, respectively). These findings implicated that miR-24 high regulation is a common event in AML with t(8;21), and it might serve as a novel and selective therapeutic target for the treatment of AML with t(8;21). PMID:25550847

  20. MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets.

    PubMed

    Su, R; Lin, H-S; Zhang, X-H; Yin, X-L; Ning, H-M; Liu, B; Zhai, P-F; Gong, J-N; Shen, C; Song, L; Chen, J; Wang, F; Zhao, H-L; Ma, Y-N; Yu, J; Zhang, J-W

    2015-06-01

    MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy. PMID:25174404

  1. Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury.

    PubMed

    Roy, Sanchari; Benz, Fabian; Alder, Jan; Bantel, Heike; Janssen, Joern; Vucur, Mihael; Gautheron, Jeremie; Schneider, Anne; Schüller, Florian; Loosen, Sven; Luedde, Mark; Koch, Alexander; Tacke, Frank; Luedde, Tom; Trautwein, Christian; Roderburg, Christoph

    2016-07-01

    miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury. PMID:27129188

  2. Isoflurane attenuates LPS-induced acute lung injury by targeting miR-155-HIF1-alpha.

    PubMed

    Hu, Rong; Zhang, Ying; Yang, Xiaohua; Yan, Jia; Sun, Yu; Chen, Zhifeng; Jiang, Hong

    2015-01-01

    Isoflurane alleviates the inflammatory response in endotoxin-induced acute lung injury (ALI). In this study, we investigated the protective mechanism of isoflurane postconditioning in lipopolysaccharide (LPS)induced ALI. Exposure to isoflurane decreased miR-155 and upregulated HIF-1 alpha and HO-1 mRNA and protein. The effects of isoflurane on HIF-1 alpha mRNA and protein could be inhibited by overexpression of miR-155. Furthermore, mice overexpressing miR-155 had higher levels of TNF-alpha and IL-1 beta in BALF when exposed to isoflurane after LPS challenge.Conversely, downregulation of miR-155 promoted isoflurane effects on HIF-1 alpha expression. These results suggest that isoflurane posttreatment hr alleviates LPS-induced ALI and cell injury by triggering miR-155-HIF-1 alpha pathway, leading to upregulation of HO-1. PMID:25553444

  3. Intracoronary administration of anisodamine and nicorandil in individuals undergoing primary percutaneous coronary intervention for acute inferior myocardial infarction: A randomized factorial trial

    PubMed Central

    CHEN, CHUNHONG; FU, XIANGHUA; LI, WEI; JIA, XINWEI; BAI, SHIRU; GENG, WEI; XING, KUN

    2015-01-01

    In acute inferior myocardial infarction (AIMI), numerous conventional drugs that are used to improve the myocardial microcirculation can significantly reduce blood pressure (BP) and coronary perfusion pressure, aggravate bradyarrhythmia and cause a deterioration in the hemodynamic state of the whole body, which greatly limits the application of these drugs in clinical settings. The aim of the present study was to assess the effect of anisodamine and nicorandil regimens on the prevention of no-reflow (NR) and the amelioration of myocardial reperfusion in patients with AIMI undergoing primary percutaneous coronary intervention (PCI). A total of 104 consecutive patients with AIMI were included in this study and randomly assigned to one of four groups: A (control group), B (anisodamine group), C (nicorandil group) and D (anisodamine and nicorandil group). Patients underwent PCI via transradial artery access and the angiographic results were evaluated. Coronary diastolic BP (DBP) and systolic and mean BPs were measured by invasive catheterization. The primary end-point was a post-PCI Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG) of 3. Composite end-points (mortality + new MI + target vessel revascularization) were evaluated during the hospital stay and 30 days after discharge. Following the procedure, the proportion of patients achieving TMPG 3 was significantly higher in group D than that in the other groups (P=0.014); furthermore, the incidence of a postprocedural TIMI score of 3 was the highest in group D. Three days after the procedure, the peak creatine kinase-MB and cardiac troponin I levels were the lowest and the left ventricular ejection fraction was the highest in group D. A thrombus score of 3/4 and low DBP were the independent risk factors for poor myocardial reperfusion (expressed as TMPG <3), while 2 mg anisodamine plus 2 mg nicorandil prior to PCI was protective for optimal myocardial reperfusion following the procedure

  4. Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150 Nanoparticles.

    PubMed

    Jiang, Xi; Bugno, Jason; Hu, Chao; Yang, Yang; Herold, Tobias; Qi, Jun; Chen, Ping; Gurbuxani, Sandeep; Arnovitz, Stephen; Strong, Jennifer; Ferchen, Kyle; Ulrich, Bryan; Weng, Hengyou; Wang, Yungui; Huang, Hao; Li, Shenglai; Neilly, Mary Beth; Larson, Richard A; Le Beau, Michelle M; Bohlander, Stefan K; Jin, Jie; Li, Zejuan; Bradner, James E; Hong, Seungpyo; Chen, Jianjun

    2016-08-01

    Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3 We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. Cancer Res; 76(15); 4470-80. ©2016 AACR. PMID:27280396

  5. miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia.

    PubMed

    Jiang, Xi; Hu, Chao; Arnovitz, Stephen; Bugno, Jason; Yu, Miao; Zuo, Zhixiang; Chen, Ping; Huang, Hao; Ulrich, Bryan; Gurbuxani, Sandeep; Weng, Hengyou; Strong, Jennifer; Wang, Yungui; Li, Yuanyuan; Salat, Justin; Li, Shenglai; Elkahloun, Abdel G; Yang, Yang; Neilly, Mary Beth; Larson, Richard A; Le Beau, Michelle M; Herold, Tobias; Bohlander, Stefan K; Liu, Paul P; Zhang, Jiwang; Li, Zejuan; He, Chuan; Jin, Jie; Hong, Seungpyo; Chen, Jianjun

    2016-01-01

    MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy. PMID:27116251

  6. Circulating miR-122-5p as a potential novel biomarker for diagnosis of acute myocardial infarction

    PubMed Central

    Yao, Xin-Liang; Lu, Xue-Li; Yan, Cheng-Yun; Wan, Qi-Lin; Cheng, Guan-Chang; Li, Yan-Ming

    2015-01-01

    Background: MicroRNAs (miRNAs) play key roles in cardiac development, and the expression of miRNAs is altered in the diseased heart. The aim of this study was to explore the value of circulating microRNA-122-5p (miR-122-5p) as a potential biomarker for acute myocardial infarction (AMI). Methods: Plasma samples from 50 patients with AMI and 39 healthy adults (non-AMI controls) were collected. The abundance of circulating miR-122-5p was measured using quantitative real-time PCR (qRT-PCR). The cTnI concentrations of these samples were analyzed by ELISA. Results: Our findings revealed that circulating miR-122-5p expression were increased in AMI patients at 4 h, 8 h, 12 h, and 24 h by contrast to those non-AMI controls and displayed similar trends to that of cTnI concentrations in AMI patients. Further study showed that there is a high correlation between circulating miR-122-5p and cTnI concentrations. At last, the receiver operating characteristic (ROC) curve was performed and showed that circulating miR-122-5p had considerable diagnostic accuracy for AMI with an area under curve (AUC) of 0.855. Conclusions: Our results implied that circulating miR-122-5p could be a potential biomarker for AMI. PMID:26884877

  7. Overexpression of miR-378 is frequent and may affect treatment outcomes in patients with acute myeloid leukemia.

    PubMed

    Qian, Jun; Lin, Jiang; Qian, Wei; Ma, Ji-chun; Qian, Si-xuan; Li, Yun; Yang, Jing; Li, Jian-yong; Wang, Cui-zhu; Chai, Hai-yan; Chen, Xing-xing; Deng, Zhao-qun

    2013-07-01

    MicroRNA miR-378 plays important roles in tumorigenesis by enhancing cell survival, reducing apoptosis, promoting tumor growth, angiogenesis and promoting cell migration and invasion. Abnormal expression of miR-378 has been observed in various types of cancers. The aim of this study was to investigate the expression status of miR-378 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. miR-378 overexpression was identified in 26 of 84 (31%) AML patients. The patients with miR-378 overexpression had lower hemoglobin level than those without miR-378 overexpression (66 versus 78 g/L, respectively, P=0.010). The frequency of miR-378 overexpression in FAB-M2 subtype was higher than other subtypes (44% versus 20%, P=0.032). Moreover, the frequency of miR-378 overexpression was higher in patients with t(8;21) than in others (64% versus 24%, P=0.012). The status of miR-378 expression was not correlated with the mutations of eight genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and U2AF1). The difference in relapse-free survival was observed between patients with and without miR-378 overexpression (P=0.049). These findings suggest that miR-378 up-regulation is a common event and might have an adverse impact on prognosis in AML. PMID:23582927

  8. Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

    PubMed Central

    Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

    2014-01-01

    Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. PMID:25013367

  9. Does Intravenous Administration of Recombinant Tissue Plasminogen Activator for Ischemic Stroke can Cause Inferior Myocardial Infarction?

    PubMed Central

    Almasi, Mostafa; Razmeh, Saeed; Habibi, Amir Hassan; Rezaee, Amir Hassan

    2016-01-01

    Recombinant tissue plasminogen activator (rTPA) is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI) is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved. PMID:27441068

  10. MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia.

    PubMed

    Correia, Nádia C; Fragoso, Rita; Carvalho, Tânia; Enguita, Francisco J; Barata, João T

    2016-01-01

    Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1-positive cell line extends mouse survival in a xenotransplant model of human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness. PMID:27550837

  11. MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia

    PubMed Central

    Correia, Nádia C.; Fragoso, Rita; Carvalho, Tânia; Enguita, Francisco J.; Barata, João T.

    2016-01-01

    Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1-positive cell line extends mouse survival in a xenotransplant model of human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness. PMID:27550837

  12. Catheter-Directed Thrombolysis of Acute Deep Vein Thrombosis in the Lower Extremity of a Child with Interrupted Inferior Vena Cava

    SciTech Connect

    Oguzkurt, Levent Ozkan, Ugur; Tercan, Fahri; Koc, Zafer

    2007-04-15

    We present the case of a 14-year-old girl who developed acute deep vein thrombosis (DVT) in her right lower extremity. Laboratory testing revealed protein S deficiency, and the patient's father also had this abnormality with a history of lower extremity DVT. Manual thromboaspiration followed by catheter-directed thrombolysis resulted in total clearance of all thrombi. Computed tomography and later venography revealed an interrupted inferior vena cava. Catheter-directed thrombolysis is an established treatment for adults with acute DVT. To the best of our knowledge, this report is the first to describe catheter-directed thrombolysis in a pediatric patient with lower extremity DVT. Our results suggest that catheter-directed thrombolysis is safe and effective for use in selected older children and adolescents with acute DVT in the lower extremity.

  13. MiR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1.

    PubMed

    Sun, Yan-Ping; Lu, Fei; Han, Xiao-Yu; Ji, Min; Zhou, Ying; Zhang, A-Min; Wang, Hong-Chun; Ma, Dao-Xin; Ji, Chun-Yan

    2016-05-01

    Although microRNAs have been elaborated to participate in various physiological and pathological processes, their functions in TRAIL resistance of acute myeloid leukemia (AML) remain obscure. In this study, we detected relatively lower expression levels of miR-424&27a in TRAIL-resistant and semi-resistant AML cell lines as well as newly diagnosed patient samples. Overexpression of miR-424&27a, by targeting the 3'UTR of PLAG1, enhanced TRAIL sensitivity in AML cells. Correspondingly, knockdown of PLAG1 sensitized AML cells to TRAIL-induced apoptosis and proliferation inhibition. We further found that PLAG1 as a transcription factor could reinforce Bcl2 promoter activity, causing its upregulation at the mRNA level. Both downregulated PLAG1 and elevated expression of miR-424&27a led to Bcl2 downregulation and augmented cleavage of Caspase8, Caspase3 and PARP in the presence of TRAIL. Restoration of Bcl2 could eliminate their effects on AML TRAIL sensitization. Overall, we propose that miR-424&27a and/or PLAG1 might serve as novel therapeutic targets in AML TRAIL therapy. PMID:27013583

  14. Circulating microRNAs as mirrors of acute coronary syndromes: MiRacle or quagMire?

    PubMed

    Li, Jin; Xu, Jiahong; Cheng, Yan; Wang, Fei; Song, Yang; Xiao, Junjie

    2013-11-01

    Acute coronary syndrome (ACS), a leading cause of morbidity and mortality worldwide, is among the most serious cardiovascular diseases. Exploring novel approaches, which can complement and improve current strategies for ACS, is continuous. MicroRNAs (miRNAs) are a novel class of small, short non-coding RNA that post-transcriptionally regulate genes. The tissue- or cell-specific distribution features of miRNAs and its merit of stably existing in serum and plasma make them attractive biomarkers for ACS. An early and accurate diagnosis is the pre-requisite to facilitate rapid decision making and treatment and therefore improve outcome in ACS patients. This review highlights and summarizes recent studies using circulating miRNAs as novel biomarkers for ACS including its role in diagnosis, prediction, prognosis and reaction to therapy. In addition, we also discuss the potential function of miRNAs as extracellular communicators in cell-to-cell communication. Large multicentre studies are highly needed to pave the road for using circulating miRNAs as biomarkers for ACS from the bench to the bedside. Considering the advantageous properties and the continuously increasing number of studies, circulating miRNAs definitely have the potential to be reasonable diagnostic tools once their infancy has passed. PMID:24188699

  15. A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery.

    PubMed

    Altas, Yakup; Ulugg, Ali Veysel

    2016-01-01

    ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient's history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. PMID:27555777

  16. A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery

    PubMed Central

    Altas, Yakup; Ulugg, Ali Veysel

    2016-01-01

    ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient’s history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. PMID:27555777

  17. Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

    PubMed Central

    Ställberg, Björn; Selroos, Olof; Vogelmeier, Claus; Andersson, Eva; Ekström, Tommy; Larsson, Kjell

    2009-01-01

    Background Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation. Methods This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home. A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined. Results Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified. Conclusion High dose budesonide/formoterol was as

  18. Evaluating Diagnostic and Prognostic Value of Plasma miRNA133a in Acute Chest Pain Patients Undergoing Coronary Angiography

    PubMed Central

    Ke-Gang, Jia; Zhi-Wei, Li; Xin, Zhang; Jing, Wang; Ping, Shi; Xue-Jing, Han; Hong-Xia, Tang; Xin, Tang; Xiao-Cheng, Liu

    2016-01-01

    Abstract Circulating microRNA has recently emerged as a promising biomarker for cardiovascular disease. This study sought to evaluate the diagnostic and prognostic value of circulating miR-133a as a marker of acute myocardial infarction in acute chest pain patients undergoing coronary angiography. Plasma was collected from 312 patients with chest pain on admission in the emergency department and 67 healthy controls. MiR-133a was detected using real-time quantitative PCR and enhanced accu-TnI, creatinine kinase-MB mass, and myoglobin were measured by immunoassay. End-point events (serious adverse cardiovascular events which require hospitalization or cardiovascular death) were examined in the AMI (acute myocardical infarction) group within 1, 6, 12, and 24 months. The miR-133a level was higher in AMI patients than in non-AMI patients (P < 0.001). In the ROC analysis, the sensitivity of miR-133a in diagnosis of AMI is 0.61 and the specificity is 0.68. In the prognostic analysis, only 1 endpoint event was observed in the non-AMI group; the amount of cases with end-point events in the AMI group at 1,6,12, and 24 months were 8, 19, 28, and 35, respectively. The cutoff value of miR-133a was determined using the median value of the AMI group and separated the patients into a positive group and a negative group. The Kaplan–Meier survival curve showed no significant difference in survival was detected in AMI patients between the miR-133a positive group and negative group after follow-up (12-month: x2 = 1.353, P = 0.245; 24-month: x2 = 3.722, P = 0.054). After adjusting for age, gender, Killip classes, prior myocardiac infarction history, myoglobin, LVEF (left ventricular ejection fraction), diabetes, hypertension, smoking and systolic blood pressure, miR133a had a significant association with the risk of events at 12 months (HR = 2.869, P = 0.024) and 24 months (HR = 3.936, P = 0.001). In patients undergoing coronary angiography

  19. miRNA-149* promotes cell proliferation and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia.

    PubMed

    Fan, Sheng-Jin; Li, Hui-Bo; Cui, Gang; Kong, Xiao-Lin; Sun, Li-Li; Zhao, Yan-Qiu; Li, Ying-Hua; Zhou, Jin

    2016-02-01

    MicroRNA-149* (miRNA-149*) functions as an oncogenic regulator in human melanoma. However, the effect of miRNA-149* on T-cell acute lymphoblastic leukemia (T-ALL) is unclear. Here we aimed to analyze the effects of miRNA-149* on in vitro T-ALL cells and to uncover the target for miRNA-149* in these cells. The miRNA-149* level was determined in multiple cell lines and bone marrow cells derived from patients with T-ALL, B acute lymphoblastic leukemia (B-ALL), acute myelocytic leukemia (AML), and healthy donors. We found that miRNA-149* was highly expressed in T-ALL cell lines and T-ALL patients' bone marrow samples. JunB was identified as a direct target of miR-149*. miRNA-149* mimics downregulated JunB levels in Molt-4 and Jurkat cells, while miRNA-149* inhibitors dramatically upregulated JunB expression in these cells. miRNA-149* mimics promoted proliferation, decreased the proportion of cells in G1 phase, and reduced cell apoptosis in T-ALL cells, while miRNA-149* inhibitors prevented these effects. miRNA-149* mimics downregulated p21 and upregulated cyclinD1, 4EBP1, and p70s6k in Molt-4 and Jurkat cells. Again, inhibitors prevented these effects. Our findings demonstrate that miRNA-149* may serve as an oncogenic regulator in T-ALL by negatively regulating JunB. PMID:26725775

  20. Therapeutic hypothermia for the treatment of acute myocardial infarction-combined analysis of the RAPID MI-ICE and the CHILL-MI trials.

    PubMed

    Erlinge, David; Götberg, Matthias; Noc, Marko; Lang, Irene; Holzer, Michael; Clemmensen, Peter; Jensen, Ulf; Metzler, Bernhard; James, Stefan; Bøtker, Hans Erik; Omerovic, Elmir; Koul, Sasha; Engblom, Henrik; Carlsson, Marcus; Arheden, Håkan; Östlund, Ollie; Wallentin, Lars; Klos, Bradley; Harnek, Jan; Olivecrona, Göran K

    2015-06-01

    In the randomized rapid intravascular cooling in myocardial infarction as adjunctive to percutaneous coronary intervention (RAPID MI-ICE) and rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction CHILL-MI studies, hypothermia was rapidly induced in conscious patients with ST-elevation myocardial infarction (STEMI) by a combination of cold saline and endovascular cooling. Twenty patients in RAPID MI-ICE and 120 in CHILL-MI with large STEMIs, scheduled for primary percutaneous coronary intervention (PCI) within <6 hours after symptom onset were randomized to hypothermia induced by rapid infusion of 600-2000 mL cold saline combined with endovascular cooling or standard of care. Hypothermia was initiated before PCI and continued for 1-3 hours after reperfusion aiming at a target temperature of 33°C. The primary endpoint was myocardial infarct size (IS) as a percentage of myocardium at risk (IS/MaR) assessed by cardiac magnetic resonance imaging at 4±2 days. Patients randomized to hypothermia treatment achieved a mean core body temperature of 34.7°C before reperfusion. Although significance was not achieved in CHILL-MI, in the pooled analysis IS/MaR was reduced in the hypothermia group, relative reduction (RR) 15% (40.5, 28.0-57.6 vs. 46.6, 36.8-63.8, p=0.046, median, interquartile range [IQR]). IS/MaR was predominantly reduced in early anterior STEMI (0-4h) in the hypothermia group, RR=31% (40.5, 28.8-51.9 vs. 59.0, 45.0-67.8, p=0.01, median, IQR). There was no mortality in either group. The incidence of heart failure was reduced in the hypothermia group (2 vs. 11, p=0.009). Patients with large MaR (>30% of the left ventricle) exhibited significantly reduced IS/MaR in the hypothermia group (40.5, 27.0-57.6 vs. 55.1, 41.1-64.4, median, IQR; hypothermia n=42 vs. control n=37, p=0.03), while patients with MaR<30% did not show effect of hypothermia (35

  1. Acute endocrine and nutritional co-regulation of the hepatic omy-miRNA-122b and the lipogenic gene fas in rainbow trout, Oncorhynchus mykiss.

    PubMed

    Mennigen, Jan A; Plagnes-Juan, Elisabeth; Figueredo-Silva, Claudia A; Seiliez, Iban; Panserat, Stéphane; Skiba-Cassy, Sandrine

    2014-03-01

    Hepatic lipogenesis represents a crucial part of intermediary metabolism and is acutely regulated by endocrine factors and nutrients. The liver-specific and highly abundant microRNA-122 has emerged as a powerful regulator of lipogenesis in higher vertebrates, but little is known about its endocrine and nutritional regulation. In this study, we investigated the hypothesis that insulin regulates hepatic expression of omy-miRNA-122 isomiRNAs (omy-miRNA-122a and omy-miRNA-122b) by using in vivo and in vitro approaches. Since the hepatic insulin pathway and lipogenesis are acutely regulated by dietary macronutrient ratios in rainbow trout, we further investigated the effect of single meals with altered carbohydrate/protein ratio and lipid/protein ratio on the postprandial expression of omy-miRNA-122 isomiRNAs. Insulin acutely induced omy-miRNA-122b expression in vivo and in vitro. Conversely, a single meal with increased lipid to protein ratio acutely decreased expression of both omy-miRNA-122 isomiRNAs. As a direct proof of lipogenic effects of miRNA-122 is currently still lacking in fish, we investigated the correlated expression between omy-miRNA-122 isomiRNAs and the rate-limiting lipogenic gene fas, an indirect target gene of miRNA-122 in mammals. Our results show a significant positive correlation of omy-miRNA-122b and fas, consistent with a potential evolutionary conserved role for miRNA-122 in the regulation of postprandial lipogenesis in trout. PMID:24333236

  2. Traumeel vs. diclofenac for reducing pain and improving ankle mobility after acute ankle sprain: A multicentre, randomised, blinded, controlled and non-inferiority trial

    PubMed Central

    González de Vega, C; Speed, C; Wolfarth, B; González, J

    2013-01-01

    Background Acute ankle sprains are common and activity limiting injuries, and topical diclofenac gel has proven efficacy in alleviating pain and restoring function. This trial aimed to compare a topical natural agent, Traumeel with topical diclofenac gel (1%) in the management of acute ankle sprain. Methods This prospective, multicentre, randomised, blinded, active-control and non-inferiority study involved 449 physically active adults sustaining unilateral grade 1 or 2 ankle sprain within the past 24 h. Participants were randomised to receive 2 g of Traumeel ointment (T-O) (n = 152) or Traumeel gel (T-G) (n = 150) or diclofenac gel (D-G) (n = 147), administered topically to the ankle three times a day for 14 days, with 6-weeks follow up. Results Day 7 median percentage reductions in Visual Analogue Scale pain score were 60.6%, 71.1% and 68.9% for the T-O, T-G and D-G groups, respectively. Total pain relief was reported by 12 (8.5%), 7 (5.0%) and 8 (5.9%) participants in each group, respectively. Median improvements in Foot and Ankle Ability Measure Activities of Daily Living subscale score were 26.2, 26.2 and 25.0 points for T-O, T-G and D-G groups, respectively. Mann–Whitney effect sizes and lower bound confidence intervals demonstrated non-inferiority of Traumeel vs. diclofenac for reducing pain and functional improvement. At 6 weeks, participants reported total pain relief and normal functioning. Adverse events (n = 43) were reported by 31/447 participants (6.9%). Treatments were equally well tolerated. Conclusions T-O and T-G decreased pain and improved joint function to the same extent as D-G in acute ankle sprain, and were well tolerated. PMID:23889885

  3. Aberrant Left Inferior Bronchial Artery Originating from the Left Gastric Artery in a Patient with Acute Massive Hemoptysis

    SciTech Connect

    Jiang, Sen Sun, Xi-Wen Yu, Dong Jie, Bing

    2013-10-15

    Massive hemoptysis is a life-threatening condition, and the major source of bleeding in this condition is the bronchial circulation. Bronchial artery embolization is a safe and effective treatment for controlling hemoptysis. However, the sites of origin of the bronchial arteries (BAs) have numerous anatomical variations, which can result in a technical challenge to identify a bleeding artery. We present a rare case of a left inferior BA that originated from the left gastric artery in a patient with recurrent massive hemoptysis caused by bronchiectasis. The aberrant BA was embolized, and hemoptysis has been controlled for 8 months.

  4. Genetic mutational profiling analysis of T cell acute lymphoblastic leukemia reveal mutant FBXW7 as a prognostic indicator for inferior survival.

    PubMed

    Yuan, Lan; Lu, Ling; Yang, Yongchen; Sun, Hengjuan; Chen, Xi; Huang, Yi; Wang, Xingjuan; Zou, Lin; Bao, Liming

    2015-11-01

    T cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplasm for which there are currently no adequate biomarkers for developing risk-adapted therapeutic regimens to improve the treatment outcome. In this prospective study of 83 Chinese patients (54 children and 29 adults) with de novo T-ALL, we analyzed mutations in 11 T-ALL genes: NOTCH1, FBXW7, PHF6, PTEN, N-RAS, K-RAS, WT1, IL7R, PIK3CA, PIK3RA, and AKT1. NOTCH1 mutations were identified in 51.9 and 37.9 % of pediatric and adult patients, respectively, and these patients showed improved overall survival (OS) and event-free survival (EFS). The FBXW7 mutant was present in 25.9 and 6.9 % of pediatric and adult patients, respectively, and was associated with inferior OS and EFS in pediatric T-ALL. Multivariate analysis revealed that mutant FBXW7 was an independent prognostic indicator for inferior EFS (hazard ratio [HR] 4.38; 95 % confidence interval [CI] 1.15-16.71; p = 0.03) and tended to be associated with reduced OS (HR 2.81; 95 % CI 0.91-8.69; p = 0.074) in pediatric T-ALL. Mutant PHF6 was present in 13 and 20.7 % of our childhood and adult cohorts, respectively, while PTEN mutations were noted in 11.1 % of the pediatric patients. PTEN and NOTCH1 mutations were almost mutually exclusive, while IL7R and WT1 mutations were rare in pediatric T-ALL and PTPN11 and AKT1 mutations were infrequent in adult T-ALL. This study revealed differences in the mutational profiles of pediatric and adult T-ALL and suggests mutant FBXW7 as an independent prognostic indicator for inferior survival in pediatric T-ALL. PMID:26341754

  5. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    SciTech Connect

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  6. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.

    PubMed

    Kumar, V; Palermo, R; Talora, C; Campese, A F; Checquolo, S; Bellavia, D; Tottone, L; Testa, G; Miele, E; Indraccolo, S; Amadori, A; Ferretti, E; Gulino, A; Vacca, A; Screpanti, I

    2014-12-01

    Notch signaling deregulation is linked to the onset of several tumors including T-cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA) expression is also associated with several cancers, including leukemias. However, the transcriptional regulators of miRNAs, as well as the relationships between Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs regulated by Notch pathway, we performed microarray-based miRNA profiling of several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated by overexpressing or silencing Notch3, we focused our attention on miR-223, whose putative promoter analysis revealed a conserved RBPjk binding site, which was nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays on the promoter region of miR-223 show that both Notch and NF-kB are novel coregulatory signals of miR-223 expression, being able to activate cooperatively the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines. Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223 inhibition prevents T-ALL resistance to γ-secretase inhibitor (GSI) treatment, suggesting that miR-223 could be involved in GSI sensitivity and its inhibition may be exploited in target therapy protocols. PMID:24727676

  7. miRNA-dysregulation associated with tenderness variation induced by acute stress in angus cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3 untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cat...

  8. miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia.

    PubMed

    Nucera, Silvia; Giustacchini, Alice; Boccalatte, Francesco; Calabria, Andrea; Fanciullo, Cristiana; Plati, Tiziana; Ranghetti, Anna; Garcia-Manteiga, Jose; Cittaro, Davide; Benedicenti, Fabrizio; Lechman, Eric R; Dick, John E; Ponzoni, Maurilio; Ciceri, Fabio; Montini, Eugenio; Gentner, Bernhard; Naldini, Luigi

    2016-06-13

    MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden. PMID:27300437

  9. Prehospital Nitroglycerin Safety in Inferior ST Elevation Myocardial Infarction.

    PubMed

    Robichaud, Laurie; Ross, Dave; Proulx, Marie-Hélène; Légaré, Sébastien; Vacon, Charlene; Xue, Xiaoqing; Segal, Eli

    2016-01-01

    Patients with inferior ST elevation myocardial infarction (STEMI), associated with right ventricular infarction, are thought to be at higher risk of developing hypotension when administered nitroglycerin (NTG). However, current basic life support (BLS) protocols do not differentiate location of STEMI prior to NTG administration. We sought to determine if NTG administration is more likely to be associated with hypotension (systolic blood pressure < 90 mmHg) in inferior STEMI compared to non-inferior STEMI. We conducted a retrospective chart review of prehospital patients with chest pain of suspected cardiac origin and computer-interpreted prehospital ECGs indicating "ACUTE MI." We included all local STEMI cases identified as part of our STEMI registry. Univariate analysis was used to compare differences in proportions of hypotension and drop in systolic blood pressure ≥ 30 mmHg after nitroglycerin administration between patients with inferior wall STEMI and those with STEMI in another region (non-inferior). Multiple variable logistic regression analysis was also used to assess the study outcomes while controlling for various factors. Over a 29-month period, we identified 1,466 STEMI cases. Of those, 821 (56.0%) received NTG. We excluded 16 cases because of missing data. Hypotension occurred post NTG in 38/466 inferior STEMIs and 30/339 non-inferior STEMIs, 8.2% vs. 8.9%, p = 0.73. A drop in systolic blood pressure ≥ 30 mmHg post NTG occurred in 23.4% of inferior STEMIs and 23.9% of non-inferior STEMIs, p = 0.87. Interrater agreement for chart review of the primary outcome was excellent (κ = 0.94). NTG administration to patients with chest pain and inferior STEMI on their computer-interpreted electrocardiogram is not associated with a higher rate of hypotension compared to patients with STEMI in other territories. Computer interpretation of inferior STEMI cannot be used as the sole predictor for patients who may be at higher risk for hypotension following NTG

  10. Whether Circulating miRNAs or miRNA-Carriers Serve as Biomarkers for Acute Myocardial Infarction.

    PubMed

    Zhu, Hongyan; Fan, Guo-Chang

    2013-01-01

    Acute myocardial infarction (AMI) remains a major cause of death in the US. An early and reliable diagnosis may warrant immediate initiation of reperfusion therapy to potentially improve the survival rate among the AMI patients. Currently, cardiac troponins (i.e. cTnT and cTnI) and creatine kinase MB (CK-MB) are widely used for AMI diagnosis. However, elevation of these biomarkers is also observed in human patients with myocarditis, aortic dissection, pulmonary embolism, congestive heart failure and renal failure. Furthermore, measurable amounts of troponin proteins are usually not released from damaged myocardium before 4 to 8 h after onset of symptoms, making an early biomarker-based diagnosis of AMI rather difficult. Therefore, new biomarkers with high sensitivity and specificity in early diagnosis of AMI are greatly needed. PMID:25197685

  11. Deregulation of miR-1, miR486, and let-7a in cytogenetically normal acute myeloid leukemia: association with NPM1 and FLT3 mutation and clinical characteristics.

    PubMed

    Seyyedi, Samaneh Sadat; Soleimani, Masoud; Yaghmaie, Marjan; Ajami, Monireh; Ajami, Mansoureh; Pourbeyranvand, Shahram; Alimoghaddam, Kamran; Akrami, Seyed Mohammad

    2016-04-01

    Cytogenetically normal acute myeloid leukemia (CN-AML) constitutes the largest subgroup of AML patients that is associated with molecular alteration. MiRNAs have been shown to be aberrantly expressed in CN-AML. In addition, specific miRNA (miR) expression patterns were found to be associated with certain genetic alterations in these patients. This study investigated the expression level of miR-1, miR-486, and let-7a in 45 CN-AML patients well characterized for FLT3 and/or NPM1 mutations using real-time quantitative RT-PCR and evaluated the association between candidate miRs expression and clinical features. Our data revealed that miR-1 was significantly overexpressed in CN-AML patients, and increasing expression of miR-1 correlated with NPM1 mutation (P < 0.05) and lower hemoglobin level was also observed in patients with miR-1 overexpression (P < 0.05). The expression of miR-1 was much higher in AML-M2 compared with other subtypes. Further, we found significantly increasing miR-486 expression in 40 of 45 (89 %) CN-AML patients. There was no significant association of upregulation of miR-486 with clinical parameters. The expression level of miR-486 was increased in AML-M2 subtype. The levels of let-7a were significantly increased in CN-AML patients compared to the healthy control and significantly higher in the NPM1 ± CN-AML patients. There was no correlation detected between the level of let-7a and FLT3+. An increasing expression level of let-7a was demonstrated in M2 subtype. In addition, our data showed no significant association between increasing let-7a and clinical characteristic. Comparison of peripheral blood and bone marrow results in 30 CN-AML patients showed that there is a considerable concordance between PB and BM in the results of candidate miR levels (P < 0.001). In conclusion, further studies should also be performed to detect functional mechanism of these miRs. PMID:26526573

  12. Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia

    PubMed Central

    Khalife, J; Radomska, HS; Santhanam, R; Huang, X; Neviani, P; Saultz, J; Wang, H; Wu, Y-Z; Alachkar, H; Anghelina, M; Dorrance, A; Curfman, J; Bloomfield, CD; Medeiros, BC; Perrotti, D; Lee, LJ; Lee, RJ; Caligiuri, MA; Pichiorri, F; Croce, CM; Garzon, R; Guzman, ML; Mendler, JH; Marcucci, G

    2016-01-01

    High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluatedin clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients. PMID:25971362

  13. Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia.

    PubMed

    Khalife, J; Radomska, H S; Santhanam, R; Huang, X; Neviani, P; Saultz, J; Wang, H; Wu, Y-Z; Alachkar, H; Anghelina, M; Dorrance, A; Curfman, J; Bloomfield, C D; Medeiros, B C; Perrotti, D; Lee, L J; Lee, R J; Caligiuri, M A; Pichiorri, F; Croce, C M; Garzon, R; Guzman, M L; Mendler, J H; Marcucci, G

    2015-10-01

    High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluated in clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients. PMID:25971362

  14. miR-299-5p promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in acute promyelocytic leukemia

    PubMed Central

    WU, SHUN-QUAN; ZHANG, LANG-HUI; HUANG, HAO-BO; LI, YA-PING; NIU, WEN-YAN; ZHAN, RONG

    2016-01-01

    MicroRNAs (miRs) are often located in genomic breakpoint regions and are hypothesized to be important regulators involved in the regulation of critical cell processes, including cell apoptosis, proliferation and differentiation. miR-299 has been reported to be upregulated in acute promyelocytic leukemia (APL); however, the function and mechanistic role of miR-299 in APL remains unknown. The present study demonstrated mir-299 significantly induced cell growth and cell cycle progression at the G1/S transition in APL cells. Notably, the present study revealed that miR-299-5p induces these effects, whereas miR-299-3p does not. Additional studies demonstrated that in APL cells the tumor suppressor p21Cip1/Waf1 is a downstream target of miR-299; miR-299 binds directly to the 3′ untranslated region of p21Cip1/Waf1, and reduces protein, but not mRNA, levels of p21Cip1/Waf1. The present findings demonstrate that miR-299 exerts growth-promoting effects in APL cells through the suppression of p21Cip1/Waf1. Overall, the present study demonstrates that p21Cip1/Waf1 is a direct functional target of miR-299 in APL. PMID:27347210

  15. Accuracy of Inferior Vena Cava Ultrasound for Predicting Dehydration in Children with Acute Diarrhea in Resource-Limited Settings

    PubMed Central

    Modi, Payal; Glavis-Bloom, Justin; Nasrin, Sabiha; Guy, Allysia; Rege, Soham; Noble, Vicki E.; Alam, Nur H.; Levine, Adam C.

    2016-01-01

    Introduction Although dehydration from diarrhea is a leading cause of morbidity and mortality in children under five, existing methods of assessing dehydration status in children have limited accuracy. Objective To assess the accuracy of point-of-care ultrasound measurement of the aorta-to-IVC ratio as a predictor of dehydration in children. Methods A prospective cohort study of children under five years with acute diarrhea was conducted in the rehydration unit of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Ultrasound measurements of aorta-to-IVC ratio and dehydrated weight were obtained on patient arrival. Percent weight change was monitored during rehydration to classify children as having “some dehydration” with weight change 3–9% or “severe dehydration” with weight change > 9%. Logistic regression analysis and Receiver-Operator Characteristic (ROC) curves were used to evaluate the accuracy of aorta-to-IVC ratio as a predictor of dehydration severity. Results 850 children were enrolled, of which 771 were included in the final analysis. Aorta to IVC ratio was a significant predictor of the percent dehydration in children with acute diarrhea, with each 1-point increase in the aorta to IVC ratio predicting a 1.1% increase in the percent dehydration of the child. However, the area under the ROC curve (0.60), sensitivity (67%), and specificity (49%), for predicting severe dehydration were all poor. Conclusions Point-of-care ultrasound of the aorta-to-IVC ratio was statistically associated with volume status, but was not accurate enough to be used as an independent screening tool for dehydration in children under five years presenting with acute diarrhea in a resource-limited setting. PMID:26766306

  16. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use

    PubMed Central

    2012-01-01

    Introduction To investigate whether respiratory variation of inferior vena cava diameter (cIVC) predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure (ACF). Methods Forty patients with ACF and spontaneous breathing were included. Response to fluid challenge was defined as a 15% increase of subaortic velocity time index (VTI) measured by transthoracic echocardiography. Inferior vena cava diameters were recorded by a subcostal view using M Mode. The cIVC was calculated as follows: (Dmax - Dmin/Dmax) × 100 and then receiver operating characteristic (ROC) curves were generated for cIVC, baseline VTI, E wave velocity, E/A and E/Ea ratios. Results Among 40 included patients, 20 (50%) were responders (R). The causes of ACF were sepsis (n = 24), haemorrhage (n = 11), and dehydration (n = 5). The area under the ROC curve for cIVC was 0.77 (95% CI: 0.60-0.88). The best cutoff value was 40% (Se = 70%, Sp = 80%). The AUC of the ROC curves for baseline E wave velocity, VTI, E/A ratio, E/Ea ratio were 0.83 (95% CI: 0.68-0.93), 0.78 (95% CI: 0.61-0.88), 0.76 (95% CI: 0.59-0.89), 0.58 (95% CI: 0.41-0.75), respectively. The differences between AUC the ROC curves for cIVC and baseline E wave velocity, baseline VTI, baseline E/A ratio, and baseline E/Ea ratio were not statistically different (p = 0.46, p = 0.99, p = 1.00, p = 0.26, respectively). Conclusion In spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness. PMID:23043910

  17. Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study.

    PubMed

    Zheng, Qing-Fen; Zhang, Jing-Yun; Wu, Ju-Shan; Zhang, Ying; Liu, Mei; Bai, Li; Zhang, Jin-Yan; Zhao, Jing; Chen, Yu; Duan, Zhong-Ping; Zheng, Su-Jun

    2016-02-01

    Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV

  18. miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs.

    PubMed

    Maciejak, Agata; Kiliszek, Marek; Opolski, Grzegorz; Segiet, Agnieszka; Matlak, Krzysztof; Dobrzycki, Slawomir; Tulacz, Dorota; Sygitowicz, Grazyna; Burzynska, Beata; Gora, Monika

    2016-09-01

    Acute myocardial infarction (AMI) is a life-threatening episode of coronary artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have been reported as potential biomarkers of infarction. The present study aimed to identify differentially expressed miRNAs in patients with ST-segment elevation myocardial infarction that could be potentially dysregulated in response to early myocardial damage. miRNA expression profile analysis was performed using the Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S (Vedbaek, Denmark) on plasma samples of patients on the first day of AMI (admission) and on samples from the identical patients collected six months following AMI. Selected miRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) using independent patients with AMI and a control group of patients with a stable coronary artery disease. Thirty‑two species of plasma miRNA were differentially expressed (P<0.05) on admission compared with six months following AMI. Subsequent validation in an independent patient group confirmed that miR‑133b and miR‑22‑5p were significantly up‑regulated in the serum of patients with AMI. The receiver operating characteristic (ROC) curve analysis demonstrated a diagnostic utility for miR-22-5p, which has not previously been reported to be associated with AMI. Among the selected miRNAs, miR‑22‑5p represents a novel promising biomarker for the diagnosis of AMI. PMID:27484208

  19. Integrative computational in-depth analysis of dysregulated miRNA-mRNA interactions in drug-resistant pediatric acute lymphoblastic leukemia cells: an attempt to obtain new potential gene-miRNA pathways involved in response to treatment.

    PubMed

    Mesrian Tanha, Hamzeh; Mojtabavi Naeini, Marjan; Rahgozar, Soheila; Moafi, Alireza; Honardoost, Mohammad Amin

    2016-06-01

    Acute lymphoblastic leukemia (ALL) is the major neoplasia type among children. Despite the tremendous success of current treatment strategies, drug resistance still remains a major cause of chemotherapy failure and relapse in pediatric patients. Overwhelming evidence illustrates that microRNAs (miRNAs) act as post-transcriptional regulators of drug-resistance-related genes. The current study was aimed at how dysregulated miRNA-mRNA-signaling pathway interaction networks mediate resistance to four commonly used chemotherapy agents in pediatric ALL, including asparaginase, daunorubicin, prednisolone, and vincristine. Using public expression microarray datasets, a holistic in silico approach was utilized to investigate candidate drug resistance miRNA-mRNA-signaling pathway interaction networks in pediatric ALL. Our systems biology approach nominated significant drug resistance and cross-resistance miRNAs, mRNAs, and cell signaling pathways based on anti-correlative relationship between miRNA and mRNA expression pattern. To sum up, our systemic analysis disclosed either a new potential role of miRNAs, or a possible mechanism of cellular drug resistance, in chemotherapy resistance of pediatric ALL. The current study may shed light on predicting drug response and overcoming drug resistance in childhood ALL for subsequent generations of chemotherapies. PMID:26700663

  20. Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury.

    PubMed

    Zeng, Zhenguo; Gong, Honghan; Li, Yong; Jie, Kemin; Ding, Chengzhi; Shao, Qiang; Liu, Fen; Zhan, Yian; Nie, Cheng; Zhu, Weifeng; Qian, Kejian

    2013-09-01

    Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI. PMID:23848342

  1. Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia

    PubMed Central

    Gao, Li; Sun, Junzhong; Liu, Fang; Zhang, Hui; Ma, Yigai

    2016-01-01

    Background Although the biological insight of acute myeloid leukemia (AML) has increased in the past few years, the discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Systematical studies concerning the clinical implications and genetic correlations of HOXA9 aberrations in patients with AML are relatively promising. Materials and methods Here, we investigated mutational status and the mRNA levels of the HOXA9 gene in 258 patients with AML. Furthermore, hematological characteristics, chromosome abnormalities, and genetic mutations associated with AML were analyzed, followed by the assessment of clinical survival. Besides, the expression level and mutational status of MEIS1, a cofactor of HOXA9, were also detected in patients with AML with the aim of a deeper understanding about the homeodomain-containing transcription factors associated with hematological characteristics. Results HOXA9 and MEIS1 mutations were detected in 4.26% and 3.49% AML cases, respectively. No correlations were detected between mutation status and clinical characteristics, cytogenetic and genetic aberrations, and clinical survival. Higher HOXA9 expression levels were correlated with white blood cell count and closely associated with unfavorable karyotype as well as MLL-PTD and EZH2 mutations, whereas, there was an inverse correlation with the French–American–British M3 subtype. Compared with patients with lower HOXA9 expression levels, those with higher HOXA9 expression levels had a lower complete remission rate and inferior survivals in both AML and cytogenetically normal AML. Conclusion HOXA9 expression may serve as a promising biomarker to ameliorate a prognostic model for predicting clinical outcome and consummating individualized treatment in patients with AML. PMID:26929642

  2. Differential expression of miR-17~92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia.

    PubMed

    Scherr, M; Elder, A; Battmer, K; Barzan, D; Bomken, S; Ricke-Hoch, M; Schröder, A; Venturini, L; Blair, H J; Vormoor, J; Ottmann, O; Ganser, A; Pich, A; Hilfiker-Kleiner, D; Heidenreich, O; Eder, M

    2014-03-01

    Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL. PMID:24280866

  3. Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A).

    PubMed

    Fei, Ling; Zhang, Jun; Niu, Heping; Yuan, Chen; Ma, Xiaoli

    2016-01-01

    BACKGROUND The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. MATERIAL AND METHODS SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. RESULTS Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3' UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). CONCLUSIONS miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by. PMID:27376405

  4. Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A)

    PubMed Central

    Fei, Ling; Zhang, Jun; Niu, Heping; Yuan, Chen; Ma, Xiaoli

    2016-01-01

    Background The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. Material/Methods SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. Results Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3′ UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). Conclusions miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by. PMID:27376405

  5. Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review).

    PubMed

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Illades-Aguiar, Berenice; Leyva-Vázquez, Marco Antonio

    2016-09-01

    MicroRNAs (miRNAs) are a class of small endogenous non-coding RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis. The miRNA expression is associated with specific cytogenetic changes and can also be used to discriminate between the different subtypes of leukemia in acute lymphoblastic leukemia with common translocations, it is shown that the miRNAs have the potential to be used for clinical diagnosis and prognosis. We reviewed the roles of miRNA here with emphasis on their function in human leukemia and the mechanisms of the TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins on miRNAs expression in acute lymphoblastic leukemia. PMID:27431573

  6. Inhibition of MiR-92a May Protect Endothelial Cells After Acute Myocardial Infarction in Rats: Role of KLF2/4.

    PubMed

    Liu, Hongxia; Li, Guofen; Zhao, Wenxue; Hu, Yibo

    2016-01-01

    BACKGROUND This study was designed to investigate the effects of microRNA-92 (miR-92), Kruppel-like factor 2 (KLF2), and Kruppel-like factor 4 (KLF4) on endothelial injury after acute myocardial infarction (AMI). MATERIAL AND METHODS Blood samples were collected from 50 AMI patients for detection of cardiac troponin I (cTnI), heart-type fatty acid-binding protein (H-FABP), and von Willebrand factor (vWF). The Sprague-Dawley rat models of AMI (n=30) were established by ligating their left anterior descending coronary artery. The cardiac markers of AMI patients and rat models were analyzed with enzyme-linked immunosorbent assay and immunohistochemistry. Human umbilical vein endothelial cells were processed into 5 groups: control, negative control, miR-92a inhibitors, miR-92a inhibitors + KLF2 small interfering RNA (siRNA), and miR-92a inhibitors + KLF4 siRNA. Cell proliferation and apoptosis were detected using MTT assay and flow cytometry. RT-PCR and Western blot were conducted to analyze KLF2 and KLF4 expressions. RESULTS AMI patients exhibited significantly higher expression of both endothelial injury markers (e.g., cTnI, H-FABP, vWF) and miR-92a in blood samples, when compared with controls (P<0.05). Model rats also had similar expressional tendencies, along with lower KLF2 and KLF4 expressions (P<0.05). Further, it could be observed in cellular experiments that treatment of miR-92a mimics can further upregulate endothelial injury markers, and miR-92a and both KLF2 and KLF4 were downregulated by miR-92a mimics (all, P<0.05). Also, the luciferase activity assay confirmed the direct binding of miR-92a to 3' UTR of KLF2/4. CONCLUSIONS MiR-92a was involved in the endothelial injury process after AMI and was able to suppress KLF2 and KLF4 expression. PMID:27411964

  7. Inhibition of MiR-92a May Protect Endothelial Cells After Acute Myocardial Infarction in Rats: Role of KLF2/4

    PubMed Central

    Liu, Hongxia; Li, Guofen; Zhao, Wenxue; Hu, Yibo

    2016-01-01

    Background This study was designed to investigate the effects of microRNA-92 (miR-92), Kruppel-like factor 2 (KLF2), and Kruppel-like factor 4 (KLF4) on endothelial injury after acute myocardial infarction (AMI). Material/Methods Blood samples were collected from 50 AMI patients for detection of cardiac troponin I (cTnI), heart-type fatty acid-binding protein (H-FABP), and von Willebrand factor (vWF). The Sprague-Dawley rat models of AMI (n=30) were established by ligating their left anterior descending coronary artery. The cardiac markers of AMI patients and rat models were analyzed with enzyme-linked immunosorbent assay and immunohistochemistry. Human umbilical vein endothelial cells were processed into 5 groups: control, negative control, miR-92a inhibitors, miR-92a inhibitors + KLF2 small interfering RNA (siRNA), and miR-92a inhibitors + KLF4 siRNA. Cell proliferation and apoptosis were detected using MTT assay and flow cytometry. RT-PCR and Western blot were conducted to analyze KLF2 and KLF4 expressions. Results AMI patients exhibited significantly higher expression of both endothelial injury markers (e.g., cTnI, H-FABP, vWF) and miR-92a in blood samples, when compared with controls (P<0.05). Model rats also had similar expressional tendencies, along with lower KLF2 and KLF4 expressions (P<0.05). Further, it could be observed in cellular experiments that treatment of miR-92a mimics can further upregulate endothelial injury markers, and miR-92a and both KLF2 and KLF4 were downregulated by miR-92a mimics (all, P<0.05). Also, the luciferase activity assay confirmed the direct binding of miR-92a to 3′ UTR of KLF2/4. Conclusions MiR-92a was involved in the endothelial injury process after AMI and was able to suppress KLF2 and KLF4 expression. PMID:27411964

  8. miR-150 Deficiency Protects against FAS-Induced Acute Liver Injury in Mice through Regulation of AKT

    PubMed Central

    Chen, Weina; Han, Chang; Zhang, Jinqiang; Song, Kyoungsub; Wang, Ying; Wu, Tong

    2015-01-01

    Although miR-150 is implicated in the regulation of immune cell differentiation and activation, it remains unknown whether miR-150 is involved in liver biology and disease. This study was performed to explore the potential role of miR-150 in LPS/D-GalN and Fas-induced liver injuries by using wild type and miR-150 knockout (KO) mice. Whereas knockout of miR-150 did not significantly alter LPS/D-GalN-induced animal death and liver injury, it protected against Fas-induced liver injury and mortality. The Jo2-induced increase in serum transaminases, apoptotic hepatocytes, PARP cleavage, as well as caspase-3/7, caspase-8, and caspase-9 activities were significantly attenuated in miR-150 KO mice. The liver tissues from Jo2-treated miR-150 KO mice expressed higher levels of Akt1, Akt2, total Akt, as well as p-Akt(Ser473) compared to the wild type livers. Pretreatment with the Akt inhibitor V reversed Jo2-induced liver injury in miR-150 KO mice. The primary hepatocytes isolated from miR-150 KO mice also showed protection against Fas-induced apoptosis in vitro (characterized by less prominent PARP cleavage, less nuclear fragmentation and less caspase activation) in comparison to hepatocytes from wild type mice. Luciferase reporter assays in hepatocytes transfected with the Akt1 or Akt2 3’-UTR reporter constructs (with or without mutation of miR-150 binding site) established Akt1 and Akt2 as direct targets of miR-150. Tail vein injection of lentiviral particles containing pre-miR-150 enhanced Jo2-induced liver injury in miR-150 KO mice. These findings demonstrate that miR-150 deficiency prevents Fas-induced hepatocyte apoptosis and liver injury through regulation of the Akt pathway. PMID:26196694

  9. Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21, -200c, and -423.

    PubMed

    Pavkovic, Mira; Robinson-Cohen, Cassianne; Chua, Alicia S; Nicoara, Oana; Cárdenas-González, Mariana; Bijol, Vanesa; Ramachandran, Krithika; Hampson, Lucy; Pirmohamed, Munir; Antoine, Daniel J; Frendl, Gyorgy; Himmelfarb, Jonathan; Waikar, Sushrut S; Vaidya, Vishal S

    2016-07-01

    Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423. PMID:27122240

  10. Smad3 Inactivation and MiR-29b Upregulation Mediate the Effect of Carvedilol on Attenuating the Acute Myocardium Infarction-Induced Myocardial Fibrosis in Rat

    PubMed Central

    Lin, Qiu-Xiong; Huang, Shuai; Guo, Lin-Lin; Zhang, Meng-Zhen; Deng, Chun-Yu; Zou, Xiao; Zhong, Shi-Long; Yang, Min; Zhuang, Jian; Yu, Xi-Yong; Shan, Zhi-Xin

    2013-01-01

    Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI). The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs) in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis. PMID:24086569

  11. Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat.

    PubMed

    Zhu, Jie-Ning; Chen, Ren; Fu, Yong-Heng; Lin, Qiu-Xiong; Huang, Shuai; Guo, Lin-Lin; Zhang, Meng-Zhen; Deng, Chun-Yu; Zou, Xiao; Zhong, Shi-Long; Yang, Min; Zhuang, Jian; Yu, Xi-Yong; Shan, Zhi-Xin

    2013-01-01

    Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI). The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs) in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis. PMID:24086569

  12. The PanAM study: a multi-center, double-blinded, randomized, non-inferiority study of paracetamol versus non-steroidal anti-inflammatory drugs in treating acute musculoskeletal trauma

    PubMed Central

    2013-01-01

    Background Acute musculoskeletal trauma, including strains, sprains or contusions, occur frequently. Pain management is a crucial component of treatment. However, there is no convincing evidence which drug is superior in managing pain in these patients. The aim of the PanAM Study is to compare analgesic efficacy of three strategies of pain management: paracetamol, diclofenac, or a combination of both in patients with acute musculoskeletal trauma. Methods/design The PanAM Study is a multi-center, double blind randomized controlled trial with non-inferiority design. Included are adult patients presenting to an academic, urban Emergency Department or to a General Practice with acute, blunt, traumatic limb injury. In total, 547 patients will be included using a predefined list of exclusion criteria, to be allocated by randomization to treatment with paracetamol + placebo diclofenac, diclofenac + placebo paracetamol or paracetamol + diclofenac. The hypothesis is that paracetamol will not be inferior to treatment with diclofenac, or the combination of both. Primary outcome will be between-group differences in decrease in pain, measured with Numerical Rating Scales at baseline and at 90 minutes after study drug administration. Secondary outcomes are Numerical Rating Scales at 30 and 60 minutes and measured frequently during three consecutive days after discharge; occurrence of adverse effects; patient satisfaction and an analysis of quality of life and cost-effectiveness. Recruitment started July 2013 and is expected to last a year. Discussion With this multi-center randomized clinical trial we will investigate whether treatment with paracetamol alone is not inferior to diclofenac alone or a combination of both drugs in adult patients with acute musculoskeletal trauma. The main relevance of the trial is to demonstrate the benefits and risks of three commonly used treatment regimens for musculoskeletal trauma. Data that lead to the prevention of severe Non

  13. Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles

    PubMed Central

    Wilflingseder, Julia; Sunzenauer, Judith; Toronyi, Eva; Heinzel, Andreas; Kainz, Alexander; Mayer, Bernd; Perco, Paul; Telkes, Gábor; Langer, Robert M.; Oberbauer, Rainer

    2014-01-01

    Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI. PMID:25093671

  14. Upregulation of miR-21 by Ghrelin Ameliorates Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Inflammation and Cell Apoptosis.

    PubMed

    Zhang, Wanzhe; Shu, Liliang

    2016-08-01

    Renal ischemia-reperfusion (I/R) injury can be caused by cardiac surgery, renal vascular obstruction, and kidney transplantation, mainly leading to acute kidney injury (AKI), which is complicated by lack of effective preventative and therapeutic strategies. Ghrelin has recently been reported to possess anti-inflammatory properties in several types of cells; however, little attention has been given to the role of ghrelin in I/R-induced AKI. The aim of this study is to explore the role of ghrelin in I/R-induced AKI. In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell I/R model were successfully constructed. Ghrelin expression was increased significantly in these rat and cell models. After enhancing ghrelin level by injecting exogenous ghrelin into rats or transfecting a ghrelin-pcDNA3.1 vector into renal tubular epithelial cells, we observed that I/R-induced AKI can be ameliorated by ghrelin, as shown by alterations in histology, as well as changes in serum creatinine (SCr) level, cell apoptosis, and the levels of inflammatory factors. Based on the importance of microRNA-21 (miR-21) in renal disease and the modulation effect of ghrelin on miR-21 in gastric epithelial cells, we tested whether miR-21 participates in the protective effect of ghrelin on I/R-induced AKI. Ghrelin could upregulate the PI3K/AKT signaling pathway by increasing the miR-21 level, which led to the protective effect of ghrelin on I/R-induced AKI by inhibiting the inflammatory response and renal tubular epithelial cell apoptosis. Our research identifies that ghrelin can ameliorate I/R-induced AKI by upregulating miR-21, which advances the understanding of mechanisms by which ghrelin ameliorates I/R-induced AKI. PMID:27152763

  15. Bilateral inferior turbinate osteoma.

    PubMed

    Sahemey, R; Warfield, A T; Ahmed, S

    2016-01-01

    Osteomas are the most common benign osteoclastic tumours of the paranasal sinuses. However, nasal cavity and turbinate osteomas are extremely rare. Only nine middle turbinate, three inferior turbinate and one inferior turbinate osteoma cases have been reported to date. The present case report describes the management and follow-up of symptomatic bilateral inferior turbinate osteoma.A 60-year-old female presented with symptoms of bilateral nasal obstruction and right-sided epiphora. Radiological investigation found hypertrophic bony changes involving both inferior turbinates. The patient was managed successfully by endoscopic inferior turbinectomies in order to achieve a patent airway, with no further recurrence of tumour after 3 months postoperatively.To the best of our knowledge, this is the first reported case of bilateral inferior turbinate osteoma. We describe a safe and minimally invasive method of tumour resection, which has a better cosmetic outcome compared with other approaches. PMID:27534890

  16. Baseline low immunoglobulin A predicts inferior disease-free survival in pediatric acute myeloid leukemia and serial evaluation suggests role of immunoglobulin A in leukemogenesis.

    PubMed

    Bansal, Anuj Kumar; Vishnubhatla, Sreenivas; Kumar, Uma; Bakhshi, Sameer

    2014-05-01

    Abstract Data on serial evaluation of immunoglobulins (Ig) in pediatric AML is lacking. From April 2010 to May 2011, 45 consecutive patients with AML aged 1-18 years were prospectively enrolled along with nine healthy controls. Ig were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse. At diagnosis, Ig levels were significantly higher in patients than in healthy controls. Patienths with gum hypertrophy had low Ig levels (IgG, p = 0.007; IgA, p = 0.003; IgM, p = 0.06). Baseline Ig did not correlate with complete remission (CR). Patients who relapsed had a lower baseline IgA level than those in continuous CR (169 ± 94 g/dL vs. 310 ± 177 g/dL, p = 0.019). Patients with a low baseline IgA level (less than median) had inferior disease-free-survival (DFS) on multivariate analysis (p = 0.048). Post-induction, IgM (p < 0.001) and IgA (p = 0.048) were significantly reduced as compared to their baseline values. On serial follow-up in patients who were in continuous CR, there was a significant decrease in IgA from post-induction until 6 months after treatment completion. This is the first study to evaluate the trend of humoral immunity in sequential pediatric patients with AML. Our study demonstrates that in pediatric AML, baseline Ig were higher than in controls. Gum hypertrophy was observed in patients with low Ig (IgA and IgG) levels. Relatively lower baseline IgA predicted disease relapse and inferior DFS. On serial follow-up, IgA significantly decreased in those who continued to stay in CR but not in patients who relapsed, suggesting an association of IgA with leukemogenesis. PMID:23865831

  17. Hypermethylation and down-regulation of DLEU2 in paediatric acute myeloid leukaemia independent of embedded tumour suppressor miR-15a/16-1

    PubMed Central

    2014-01-01

    Background Acute Myeloid Leukaemia (AML) is a highly heterogeneous disease. Studies in adult AML have identified epigenetic changes, specifically DNA methylation, associated with leukaemia subtype, age of onset and patient survival which highlights this heterogeneity. However, only limited DNA methylation studies have elucidated any associations in paediatric AML. Methods We interrogated DNA methylation on a cohort of paediatric AML FAB subtype M5 patients using the Illumina HumanMethylation450 (HM450) BeadChip, identifying a number of target genes with p <0.01 and Δβ >0.4 between leukaemic and matched remission (n = 20 primary leukaemic, n = 13 matched remission). Amongst those genes identified, we interrogate DLEU2 methylation using locus-specific SEQUENOM MassARRAY® EpiTYPER® and an increased validation cohort (n = 28 primary leukaemic, n = 14 matched remission, n = 17 additional non-leukaemic and cell lines). Following methylation analysis, expression studies were undertaken utilising the same patient samples for singleplex TaqMan gene and miRNA assays and relative expression comparisons. Results We identified differential DNA methylation at the DLEU2 locus, encompassing the tumour suppressor microRNA miR-15a/16-1 cluster. A number of HM450 probes spanning the DLEU2/Alt1 Transcriptional Start Site showed increased levels of methylation in leukaemia (average over all probes >60%) compared to disease-free haematopoietic cells and patient remission samples (<24%) (p < 0.001). Interestingly, DLEU2 mRNA down-regulation in leukaemic patients (p < 0.05) was independent of the embedded mature miR-15a/16-1 expression. To assess prognostic significance of DLEU2 DNA methylation, we stratified paediatric AML patients by their methylation status. A subset of patients recorded methylation values for DLEU2 akin to non-leukaemic specimens, specifically patients with sole trisomy 8 and/or chromosome 11 abnormalities. These patients also showed

  18. Aldosterone induces NRK-52E cell apoptosis in acute kidney injury via rno-miR-203 hypermethylation and Kim-1 upregulation

    PubMed Central

    Xiao, Xiangcheng; Tang, Rong; Zhou, Xiao; Peng, Ling; Yu, Pingping

    2016-01-01

    Acute kidney injury (AKI) is characterized by an acute reduction in kidney function as identified by an increase in serum creatinine levels and reduction in urine output. Kidney injury molecule-1 (Kim-1) is a hallmark of kidney diseases, since it is typically non-detectable in the non-injured kidney, but upregulated and excreted in the urine during AKI. Aldosterone (Aldo) is a mediator of the renin-angiotensin-Aldo system with a pivotal role in the regulation of salt and extracellular fluid metabolism. In the present study, mice subjected to renal ischemia/reperfusion-induced AKI were investigated. The mice exhibited elevated levels of Aldo and angiotensin II, together with increased Kim-1 expression levels in renal tissue. Treatment of the mice with the Aldo receptor antagonist spironolactone decreased Kim-1 expression levels. These results suggest that Aldo may be associated with the expression of Kim-1 during AKI. However, the molecular mechanism underlying the role of Aldo in Kim-1 expression is unclear, and thus was investigated using NRK-52E cells. Aldo was found to induce the apoptosis of NRK-52E cells via the hypermethylation of rno-microRNA (miR)-203 and upregulation of Kim-1. In addition, luciferase reporter assays demonstrated that Kim-1 was a target gene of rno-miR-203 in NRK-52E cells. Furthermore, Aldo-induced NRK-52E cell apoptosis was reduced by treatment with pre-miR-203 and spironolactone to a greater extent when compared with either alone. The results may provide a promising diagnostic marker or novel therapeutic target for AKI. PMID:27446296

  19. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

    PubMed Central

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  20. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

    PubMed

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  1. Myocardial distribution of indium-111-antimyosin Fab in acute inferior and right ventricular infarction: comparison with technetium-99m-pyrophosphate imaging and histologic examination

    SciTech Connect

    Nakata, T.; Sakakibara, T.; Noto, T.; Shoji, T.; Tsuda, T.; Kubota, M.; Hattori, A.; Iimura, O. )

    1991-05-01

    In a postmortem study of a 69-yr-old female patient who had suffered 2 yr previously a non-Q-wave anterior infarction and who had sustained just seven days earlier a left inferior and right ventricular infarction, the distribution of {sup 111}In-antimyosin Fab was compared to the results of {sup 99}mTc-pyrophosphate imaging and histologic examination. Indium-111-antimyosin Fab imaging could not be performed because of cardiogenic shock. However, postmortem gamma scintillation counting revealed increased activities of antimyosin Fab in the inferoapical and right ventricular infarcted regions in which {sup 99}mTc-pyrophosphate positive imagings were observed; in contrast, a histologically confirmed old subendocardial anterior infarction had no definite activity. Thus, the myocardial distribution of {sup 111}In-antimyosin Fab corresponded well to the results of {sup 99}mTc scintigrams and histologic examinations in a human heart, suggesting that this technique could be useful in vivo for detecting several-day-old myocardial infarction of the right ventricle as well as the left ventricle. Tissue from the 2-yr-old infarction was not identified by this technique.

  2. Differentially expressed microRNA cohorts in seed development may contribute to poor grain filling of inferior spikelets in rice

    PubMed Central

    2014-01-01

    Background The inferior spikelets are defined to be those at portions where the grains receive less photosynthetic products during the seed development. The typical inferior spikelets are physically located on the proximal secondary branches in a rice panicle and traditionally characterized by a later flowering time and a slower grain-filling rate, compared to those so-called superior spikelets. Grains produced on the inferior spikelets are consequently under-developed and lighter in weight than those formed on the superior spikelets. MicroRNAs (miRNAs) are recognized as key players in regulating plant development through post-transcriptional gene regulations. We previously presented the evidence that miRNAs may influence grain-filling rate and played a role in determining the grain weight and yield in rice. Results In this study, further analyses of the expressed small RNAs in superior and inferior spikelets were conducted at five distinct developmental stages of grain development. Totally, 457 known miRNAs and 13 novel miRNAs were analyzed, showing a differential expression of 141 known miRNAs between superior and inferior spikelets with higher expression levels of most miRNAs associated with the superior than the inferior spikelets during the early stage of grain filling. Genes targeted by those differentially expressed miRNAs (i.e. miR156, miR164, miR167, miR397, miR1861, and miR1867) were recognized to play roles in multiple developmental and signaling pathways related to plant hormone homeostasis and starch accumulation. Conclusions Our data established a complicated link between miRNA dynamics and the traditional role of hormones in grain filling and development, providing new insights into the widely accepted concepts of the so-called superior and inferior spikelets in rice production. PMID:25052585

  3. [Ventricular Septal Perforation after Inferior Myocardial Infarction].

    PubMed

    Sato, Hisashi; Nakayama, Yoshihiro; Tanaka, Hideya; Takahashi, Baku

    2016-07-01

    We report a rare case of ventricular septal perforation (VSP) after inferior myocardial infarction. Surgical repair of VSP after inferior infarction is technically difficult because of its anatomical location. An 81-year-old female presented with dyspnea on the 8th day after percutaneous coronary intervention for acute inferior myocardial infarction. Echocardiography revealed a ventricular septal perforation. Urgent operation was performed. There was a VSP around the base of the ventricular septum. The myocardial infarction extended to the adjacent muscle of the mitral valve annulus. Two bovine pericardial patches were used in the left ventricular cavity. The patches were sewn on the mitral valve annulus which was the only normal tissue in the region. The 1st patch was used to close the VSP directly, and the 2nd patch was sutured to the normal myocardium to exclude the infracted area. No residual shunt flow was observed. The postoperative course was uneventful. PMID:27365060

  4. The p16(INK4A)/pRb pathway and telomerase activity define a subgroup of Ph+ adult Acute Lymphoblastic Leukemia associated with inferior outcome.

    PubMed

    Chien, Wei W; Catallo, Régine; Chebel, Amel; Baranger, Laurence; Thomas, Xavier; Béné, Marie-Christine; Gerland, Luc M; Schmidt, Aline; Beldjord, Kheira; Klein, Nathalie; Escoffre-Barbe, Martine; Leguay, Thibaut; Huguet, Françoise; Larosa, Fabrice; Hayette, Sandrine; Plesa, Adriana; Ifrah, Norbert; Dombret, Hervé; Salles, Gilles; Chassevent, Agnès; Ffrench, Martine

    2015-04-01

    Adult Acute Lymphoblastic Leukemia (ALL) therapies have been improved by pediatric-like approaches. However, treatment failures and relapses are common and new markers are needed to identify patients with poor prognosis in prospective trials. The p16(INK4A)/CDK4-6/pRb pathway and telomerase activity, which are implicated in cell activation and aging, were analyzed to identify new prognostic markers. Proteins of the p16(INK4A)/CDK4-6/pRb pathway and telomerase activity were analyzed in 123 adult B-cell precursor (BCP) ALL cases included in the GRAALL/GRAAPH trials. We found a significantly increased expression of p16(INK4A) in BCP-ALLs with MLL rearrangement. Telomerase activity was significantly lower in Philadelphia chromosome-negative/IKAROS-deleted (BCR-ABL1(-)/IKAROS(del)) cases compared to Philadelphia chromosome-positive (BCR-ABL1+) BCP-ALLs. In BCR-ABL1+ ALLs, high CDK4 expression, phosphorylated pRb (p-pRb) and telomerase activity were significantly associated with a shorter disease-free survival (DFS) and event-free survival (EFS). Enhanced p16(INK4A) expression was only related to a significantly shorter DFS. In vitro analyses of normal stimulated lymphocytes after short- and long-term cultures demonstrated that the observed protein variations of poor prognosis in BCR-ABL1+ ALLs may be related to cell activation but not to cell aging. For these patients, our findings argue for the development of therapeutic strategies including the addition of new lymphocyte activation inhibitors to current treatments. PMID:25675863

  5. Low-Dose (10%) Computed Tomography May Be Inferior to Standard-Dose CT in the Evaluation of Acute Renal Colic in the Emergency Room Setting

    PubMed Central

    Han, Esther; Atalla, Christopher S.; Santucci, Richard A.; O'Neil, Brian; Wynberg, Jason B.

    2016-01-01

    Abstract Introduction: Noncontrast CT is the standard of care to evaluate nephrolithiasis. We evaluated the performance of low-dose CT (LDCT) scan for evaluation of renal colic in the emergency room (ER). Materials and Methods: Patients visiting the ER with suspected nephrolithiasis received a standard-dose CT (SDCT) and an LDCT. Two urologists read the LDCTs and later they read SDCTs. Stone information was recorded on a diagram of the renal system. Findings on SDCTs and LDCTs were correlated through side-by-side comparison of the diagrams. Later, the two urologists adjudicated all nonconcordance between SDCTs and LDCTs in an unblinded manner. Results: Twenty-seven patients were included. SDCTs revealed 27 stones in 18 patients. Mean stone size was 3.81 mm. LDCTs revealed 27 stones in 18 patients with a mean stone size of 4.7 mm (p = 0.23). Overall sensitivity and specificity of LDCTs were 70% and 39%, respectively. There were eight false-positive and eight false-negative stones. All the false-positive stones on LDCTs were placed in the ureter, in which all of the corresponding SDCTs were visible calcifications outside the ureter. Of the eight false-negative stones on LDCTs, seven were visible calcifications on the SDCTs and the eighth stone was 1 mm and was not visible. Conclusion: LDCT may not perform well in the evaluation of suspected nephrolithiasis in the acute setting. LDCT scan accurately demonstrates calcifications; however, accurate placement of calcifications in or out of the urinary tract may be diminished due to impaired resolution of soft tissue structures. PMID:26728321

  6. Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells.

    PubMed

    Yamane, Keitaro; Naito, Hisamichi; Wakabayashi, Taku; Yoshida, Hironori; Muramatsu, Fumitaka; Iba, Tomohiro; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2016-01-01

    SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth. PMID:27499248

  7. Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells

    PubMed Central

    Yamane, Keitaro; Naito, Hisamichi; Wakabayashi, Taku; Yoshida, Hironori; Muramatsu, Fumitaka; Iba, Tomohiro; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2016-01-01

    SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth. PMID:27499248

  8. Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation.

    PubMed

    Gimondi, Silvia; Dugo, Matteo; Vendramin, Antonio; Bermema, Anisa; Biancon, Giulia; Cavané, Alessandra; Corradini, Paolo; Carniti, Cristiana

    2016-07-01

    Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Noninvasive diagnostic and prognostic tests for aGVHD are currently lacking, but would be beneficial in predicting aGVHD and improving the safety of allo-HSCT. Circulating microRNAs exhibit marked stability and may serve as biomarkers in several clinical settings. Here, we evaluated the use of circulating microRNAs as predictive biomarkers of aGVHD in lymphoma patients after allo-HSCT from matched unrelated donors (MUDs). After receiving informed consent, we prospectively collected plasma samples from 24 lymphoma patients before and after unmanipulated MUD allo-HSCT; microRNAs were then isolated. Fourteen patients developed aGVHD symptoms at a median of 48 days (range: 32-90) post-transplantation. Two patients developed intestinal GVHD, eight cutaneous GVHD, and four multiorgan GVHD. The microRNA expression profile was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MicroRNAs 194 and 518f were significantly upregulated in aGVHD samples compared with samples taken from non-aGVHD patients. Remarkably, these upregulated microRNAs could be detected before the onset of aGVHD. Pathway prediction analysis indicated that these microRNAs may regulate critical pathways involved in aGVHD pathogenesis. Considering the noninvasive characteristics of plasma sampling and the feasibility of detecting miRNAs after allo-HSCT using real-time polymerase chain reaction, our results indicate that circulating microRNAs have the potential to enable an earlier aGVHD diagnosis and might assist in individualizing therapeutic strategies after MUD allo-HSCT. Nevertheless, standardization of blood sampling and analysis protocols is mandatory for the introduction of miRNA profiling into routine clinical use. PMID:27013207

  9. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  10. Acute coronary syndrome

    MedlinePlus

    Heart attack-ACS; Myocardial infarction-ACS; MI-ACS; Acute MI-ACS; ST-elevation myocardial infarction-ACS; Non-ST-elevation myocardial infarction-ACS; Unstable angina-ACS; Accelerating angina-ACS; New- ...

  11. A novel fortified blended flour, corn-soy blend “plus-plus,” is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children12345

    PubMed Central

    LaGrone, Lacey N; Trehan, Indi; Meuli, Gus J; Wang, Richard J; Thakwalakwa, Chrissie; Maleta, Kenneth; Manary, Mark J

    2012-01-01

    Background: Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut paste–based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB recipe fortified with oil and dry skim milk, “CSB++,” has been developed. Objective: In this trial we compared CSB++ with 2 RUSF products for the treatment of MAM to test the hypothesis that the recovery rate achieved with CSB++ will not be >5% worse than that achieved with either RUSF. Design: We conducted a prospective, randomized, investigator-blinded, controlled noninferiority trial involving rural Malawian children aged 6–59 mo with MAM. Children received 75 kcal CSB++ · kg−1 · d−1, locally produced soy RUSF, or an imported soy/whey RUSF for ≤12 wk. Results: The recovery rate for CSB++ (n = 763 of 888; 85.9%) was similar to that for soy RUSF (795 of 806, 87.7%; risk difference: −1.82%; 95% CI: −4.95%, 1.30%) and soy/whey RUSF (807 of 918, 87.9%; risk difference: −1.99%; 95% CI: −5.10%, 1.13%). On average, children who received CSB++ required 2 d longer to recover, and the rate of weight gain was less than that with either RUSF, although height gain was the same among all 3 foods studied. Conclusions: A novel, locally produced, fortified blended flour (CSB++) was not inferior to a locally produced soy RUSF and an imported soy/whey RUSF in facilitating recovery from MAM. The recovery rate observed for CSB++ was higher than that for any other fortified blended flour tested previously. This trial is registered at clinicaltrials.gov as NCT00998517. PMID:22170366

  12. Value of a bipolar modified inferior lead in detection of inferior myocardial ischaemia.

    PubMed Central

    Jespersen, C M; Rasmussen, V

    1988-01-01

    Only bipolar leads are normally available for ambulatory monitoring. Bipolar precordial leads are reliable for detecting left coronary artery insufficiency, but may not detect changes caused by right coronary artery insufficiency. The magnitude and polarity of ST segment changes in a bipolar modified inferior lead and in CM5 were compared with those in standard electrocardiographic leads in 10 consecutive patients with acute myocardial infarction (eight inferior and two anteroseptal). The polarity of the ST segment in the modified orthogonal y lead was the same as that in aVF in all eight patients with inferior myocardial infarction and in six the size of the ST segment shift was identical in the two leads as well. In two patients the ST segment shift was larger in the modified orthogonal y lead than in aVF. In one of the two patients with anteroseptal myocardial infarction the polarity of the ST segment shift was the same in the modified orthogonal y lead and aVF. In the other patient it was slightly different. The CM5 lead did not reliably detect inferior myocardial ischaemia. A modified orthogonal y lead is suitable for the detection of inferior myocardial ischaemia. PMID:3190957

  13. Inferior Vena Cava Thrombosis.

    PubMed

    Alkhouli, Mohamad; Morad, Mohammad; Narins, Craig R; Raza, Farhan; Bashir, Riyaz

    2016-04-11

    Thrombosis of the inferior vena cava (IVC) is an under-recognized entity that is associated with significant short- and long-term morbidity and mortality. In absence of a congenital anomaly, the most common cause of IVC thrombosis is the presence of an unretrieved IVC filter. Due to the substantial increase in the number of IVC filters placed in the United States and the very low filter retrieval rates, clinicians are faced with a very large population of patients at risk for developing IVC thrombosis. Nevertheless, there is a paucity of data and societal guidelines with regards to the diagnosis and management of IVC thrombosis. This paper aims to enhance the awareness of this uncommon, but morbid, condition by providing a concise, yet comprehensive, review of the etiology, diagnostic approaches, and treatment strategies in patients with IVC thrombosis. PMID:26952909

  14. Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial

    PubMed Central

    Nair, Velu; Madan, Hemant; Sofat, Sunil; Ganguli, Prosenjit; Jacob, M.J.; Datta, Rajat; Bharadwaj, Prashant; Sarkar, R.S.; Pandit, A.J.; Nityanand, Soniya; Goel, Pravin K.; Garg, Naveen; Gambhir, Sanjay; George, Paul V.; Chandy, Sunil; Mathews, Vikram; George, Oomen K.; Talwar, K.K.; Bahl, Ajay; Marwah, Neelam; Bhatacharya, Anish; Bhargava, Balram; Airan, Balram; Mohanty, Sujata; Patel, Chetan D.; Sharma, Alka; Bhatnagar, Shinjini; Mondal, A.; Jose, Jacob; Srivastava, A.

    2015-01-01

    Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 × 108(n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion

  15. Inferior epigastric artery pseudoaneurysms

    PubMed Central

    Avula, SK

    2015-01-01

    Introduction Inferior epigastric artery (IEA) pseudoaneurysms are recognised complications of abdominal wall procedures, and a variety of approaches including surgical excision and ligation, percutaneous procedures and conservative management have been employed in treating this rare complication. Methods We describe a case of an IEA pseudoaneurysm diagnosed on computed tomography (CT) angiography, 14 days following a laparoscopic assisted low anterior resection, which was managed successfully with surgical excision and ligation. A review of the literature identified 32 reports of this complication since 1973 with 69% of cases occurring since 2000. Findings The main aetiology of IEA pseudoaneurysm was abdominal surgery (n=20); 65% of cases were attributable to abdominal wound closure or laparoscopic surgery. Two-thirds (66%) of patients presented between 11 and 63 days, and all except 1 case presented with discomfort, abdominal mass or haemodynamic instability. Colour Doppler ultrasonography was the imaging modality of choice (n=18), either alone or in combination with computed tomography and/or angiography. Surgical ligation and excision and percutaneous coil embolisation formed the mainstay of attempted treatments (69%), particularly following treatment failure using an alternative technique. Conclusions The incidence of iatrogenic IEA pseudoaneurysms appears to be increasing. Awareness of this rare complication is of clinical importance to avoid excessive morbidity for affected individuals. PMID:26263930

  16. [Two cases of acute coronary syndrome after intake of Clavis Panax].

    PubMed

    Atar, Aslı İnci; Er, Okan; Güven, Abdullah; Eryonucu, Beyhan

    2012-04-01

    Atherosclerotic cardiovascular disease is an epidemic in today's world. It is one of the most common causes of hospitalization and death. Therefore, remedies to control or heal the disease are continuously sought. In addition to scientifically researched therapies, patients frequently utilize alternative medicine. However, effective and toxic doses, metabolisms, and drug interactions of the herbs and herbal nutrition supplements are largely unknown. Herein, we present two cases with acute coronary syndrome. The first case was admitted with a diagnosis of acute inferior myocardial infaction (MI) and a stent was implanted to the occluded right coronary artery (RCA). There was a 50% stenosis in his left anterior descending artery (LAD). He was admitted with a diagnosis of non-ST elevation MI (NSTEMI) 6 months later. In the coronary angiogram, there was stent restenosis in RCA, the lesion in LAD had become thrombotic and progressed to a stenosis of 90%. He was referred to surgical revascularization. The second case was admitted for acute inferior MI and a stent was implanted to the occluded circumflex artery. Two months later, he was hospitalized for NSTEMI. Progression of coronary plaques to stenosis and stent restenosis was detected and he was referred to surgical revascularization. Both patients used the product sold as Clavis Panax, which contains panax ginseng, tribulus terrestris, and oat, after their first coronary intervention. Intake of a mixture of plant extracts may have serious consequences in humans as drug interactions and side effects are unknown. PMID:22864326

  17. MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study – A Sub-Study of the Munich Marathon Study)

    PubMed Central

    Hildebrand, Bianca; Kääb, Stefan; Hoster, Eva; Klier, Ina; Martens, Eimo; Hanley, Alan; Hanssen, Henner; Halle, Martin; Nickel, Thomas

    2016-01-01

    Introduction Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study). Methods 30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, ≥55 km/week, n = 15) and non-elite runners (NER, ≤40 km/week, n = 15). All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1), after a 10 week training period (V2), immediately after the marathon (V3) and 24h later (V4). Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point. Results MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR-30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters. Conclusion MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve

  18. Circulating microRNA profile in patients with membranous obstruction of the inferior vena cava

    PubMed Central

    SUN, GUI-XIANG; SU, YONG; LI, YING; ZHANG, YA-FENG; XU, LI-CHUN; ZU, MAO-HENG; HUANG, SHUI-PING; ZHANG, JIN-PENG; LU, ZHAO-JUN

    2016-01-01

    Membranous obstruction of the inferior vena cava (MOVC) is a common type of Budd-Chiari syndrome. However, the pathogenesis of MOVC has not been fully elucidated. Recent studies demonstrated that microRNAs (miRNAs or miRs) are involved in multiple diseases. To the best of our knowledge, specific changes in the expression of miRNAs in MOVC patients have not been previously assessed. The present study used a microarray analysis, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation, with the aim to access the miRNA expression levels in the plasma of 34 MOVC patients, compared with those in healthy controls. The results revealed a total of 16 differentially expressed miRNAs in MOVC patients. Subsequently, RT-qPCR analysis verified the statistically consistent expression of 5 selected miRNAs (miR-125a-5p, miR-133b, miR-423-5p, miR-1228-5p and miR-1266), in line with the results of the microarray analysis. These 5 miRNAs, which were described as crucial regulators in numerous biological processes and vascular diseases, may play an important role in the pathogenesis of MOVC. Bioinformatics analysis of target genes of the differentially expressed miRNAs revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for MOVC, including the ErbB, Wnt, MAPK and VEGF signaling pathway. In conclusion, miRNAs may involve in multiple signaling pathways contributing to the pathological processes of MOVC. The present study offers an intriguing new perspective on the involvement of miRNAs in MOVC; however, the precise underlying mechanisms require further validation. PMID:26997997

  19. Simulation of the Inferior Mirage

    NASA Astrophysics Data System (ADS)

    Branca, Mario

    2010-09-01

    A mirage can occur when a continuous variation in the refractive index of the air causes light rays to follow a curved path. As a result, the image we see is displaced from the location of the object. If the image appears higher in the air than the object, it is called a "superior" mirage, while if it appears lower it is called an "inferior" mirage.2 The most common example of an inferior mirage is when, on a hot day, a stretch of dry road off in the distance appears to be wet (see Fig. 1). Many lab activities have been described that simulate the formation of superior mirages. In these demonstrations light beams curve downward as they pass through a nonuni-form fluid.3-6 Much less common are laboratory demonstrations of upward-curving light rays of the kind responsible for inferior mirages. This paper describes a simple version of such a demonstration.

  20. Structure and activity of putative intronic miRNA promoters.

    PubMed

    Monteys, Alex Mas; Spengler, Ryan M; Wan, Ji; Tecedor, Luis; Lennox, Kimberly A; Xing, Yi; Davidson, Beverly L

    2010-03-01

    MicroRNAs (miRNAs) are RNA sequences of approximately 22 nucleotides that mediate post-transcriptional regulation of specific mRNAs. miRNA sequences are dispersed throughout the genome and are classified as intergenic (between genes) or intronic (embedded into a gene). Intergenic miRNAs are expressed by their own promoter, and until recently, it was supposed that intronic miRNAs are transcribed from their host gene. Here, we performed a genomic analysis of currently known intronic miRNA regions and observed that approximately 35% of intronic miRNAs have upstream regulatory elements consistent with promoter function. Among all intronic miRNAs, 30% have associated Pol II regulatory elements, including transcription start sites, CpG islands, expression sequence tags, and conserved transcription factor binding sites, while 5% contain RNA Pol III regulatory elements (A/B box sequences). We cloned intronic regions encompassing miRNAs and their upstream Pol II (miR-107, miR-126, miR-208b, miR-548f-2, miR-569, and miR-590) or Pol III (miR-566 and miR-128-2) sequences into a promoterless plasmid, and confirmed that miRNA expression occurs independent of host gene transcription. For miR-128-2, a miRNA overexpressed in acute lymphoblastic leukemia, ChIP analysis suggests dual regulation by both intronic (Pol III) and host gene (Pol II) promoters. These data support complex regulation of intronic miRNA expression, and have relevance to disregulation in disease settings. PMID:20075166

  1. A novel fortified blended flour, corn-soy blend "plus-plus," is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut-paste-based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB r...

  2. Serotonin in the inferior colliculus.

    PubMed

    Hurley, Laura M; Thompson, Ann M; Pollak, George D

    2002-06-01

    It has been recognized for some time that serotonin fibers originating in raphe nuclei are present in the inferior colliculi of all mammalian species studied. More recently, serotonin has been found to modulate the responses of single inferior colliculus neurons to many types of auditory stimuli, ranging from simple tone bursts to complex species-specific vocalizations. The effects of serotonin are often quite strong, and for some neurons are also highly specific. A dramatic illustration of this is that serotonin can change the selectivity of some neurons for sounds, including species-specific vocalizations. These results are discussed in light of several theories on the function of serotonin in the IC, and of outstanding issues that remain to be addressed. PMID:12117504

  3. Motor imagery-based skill acquisition disrupted following rTMS of the inferior parietal lobule.

    PubMed

    Kraeutner, Sarah N; Keeler, Laura T; Boe, Shaun G

    2016-02-01

    Motor imagery (MI), the mental rehearsal of motor tasks, has promise as a therapy in post-stroke rehabilitation. The potential effectiveness of MI is attributed to the facilitation of plasticity in numerous brain regions akin to those recruited for physical practice. It is suggested, however, that MI relies more heavily on regions commonly affected post-stroke, including left hemisphere parietal regions involved in visuospatial processes. However, the impact of parietal damage on MI-based skill acquisition that underlies rehabilitation remains unclear. Here, we examine the contribution of the left inferior parietal lobule (IPL) to MI using inhibitory transcranial magnetic stimulation (TMS) and an MI-based implicit sequence learning (ISL) paradigm. Participants (N = 27) completed the MI-based ISL paradigm after receiving continuous theta burst stimulation to the left IPL (TMS), or with the coil angled away from the scalp (sham). Reaction time differences (dRT) and effect sizes between implicit and random sequences assessed success of MI-based learning. Mean dRT for the sham group was 36.1 ± 28.2 ms (d = 0.71). Mean dRT in the TMS group was 7.7 ± 38.5 ms (d = 0.11). These results indicate that inhibition of the left IPL impaired MI-based learning. We conclude that the IPL and likely the visuospatial processes it mediates are critical for MI performance and thus MI-based skill acquisition or learning. Ultimately, these findings have implications for the use of MI in post-stroke rehabilitation. PMID:26487181

  4. Simulation of the Inferior Mirage

    ERIC Educational Resources Information Center

    Branca, Mario

    2010-01-01

    A mirage can occur when a continuous variation in the refractive index of the air causes light rays to follow a curved path. As a result, the image we see is displaced from the location of the object. If the image appears higher in the air than the object, it is called a "superior" mirage, while if it appears lower it is called an "inferior"…

  5. Inferior mirages: an improved model.

    PubMed

    Young, Andrew T

    2015-02-01

    A quantitative model of the inferior mirage is presented, based on a realistic temperature profile in the convective boundary layer, using Monin-Obukhov similarity theory. The top of the inverted image is determined by the logarithmic part of the profile; the bottom is the apparent horizon, which depends on optical obstruction by roughness elements. These effects of surface roughness are included in the model, which is illustrated with a simulation. The vertical magnification varies throughout the mirage, becoming infinite at Minnaert's ill-named "vanishing line"-which makes green flashes apparent to the naked eye. PMID:25967823

  6. INTERDEPENDENT SUPERIORITY AND INFERIORITY FEELINGS

    PubMed Central

    Ingham, Harrington V.

    1949-01-01

    It is postulated that in neurotic persons who have unrealistic feelings of superiority and inferiority the two are interdependent. This is a departure from the concept of previous observers that either one or the other is primary and its opposite is overcompensation. The author postulates considerable parallelism, with equal importance for each. He submits that the neurotic person forms two logic-resistant compartments for the two opposed self-estimates and that treatment which makes inroads of logic upon one compartment, simultaneously does so upon the other. Two examples are briefly reported. The neurotic benefits sought in exaggeration of capability are the same as those sought in insistence upon inferiority: Presumption of superiority at once bids for approbation and delivers the subject from the need to prove himself worthy of it in dreaded competition; exaggeration of incapability baits sympathy and makes competition unnecessary because failure is conceded. Some of the characteristics of abnormal self-estimates that distinguish them from normal are: Preoccupation with self, resistance to logical explanation of personality problems, inconsistency in reasons for beliefs in adequacy on the one hand and inadequacy on the other, unreality, rationalization of faults, and difficulty and vacillation in the selection of adequate goals. PMID:15390573

  7. Inferior vena caval masses identified by echocardiography

    NASA Technical Reports Server (NTRS)

    Sun, J. P.; Asher, C. R.; Xu, Y.; Huang, V.; Griffin, B. P.; Stewart, W. J.; Novick, A. C.; Thomas, J. D.

    1999-01-01

    The most common cause of an inferior vena caval mass is renal cell carcinoma that extends through the lumen, occurring in 47 of 62 patients (85%). Detection of an inferior vena caval mass affects the surgical approach requiring cardiopulmonary bypass for resection when the mass extends to the heart.

  8. MiR-24 Promotes the Survival of Hematopoietic Cells

    PubMed Central

    Nguyen, Tan; Rich, Audrey; Dahl, Richard

    2013-01-01

    The microRNA, miR-24, inhibits B cell development and promotes myeloid development of hematopoietic progenitors. Differential regulation of cell survival in myeloid and lymphoid cells by miR-24 may explain how miR-24′s affects hematopoietic progenitors. MiR-24 is reported to regulate apoptosis, either positively or negatively depending on cell context. However, no role for miR-24 in regulating cell death has been previously described in blood cells. To examine miR-24′s effect on survival, we expressed miR-24 via retrovirus in hematopoietic cells and induced cell death with cytokine or serum withdrawal. We observed that miR-24 enhanced survival of myeloid and B cell lines as well as primary hematopoietic cells. Additionally, antagonizing miR-24 with shRNA in hematopoietic cells made them more sensitive to apoptotic stimuli, suggesting miR-24 functions normally to promote blood cell survival. Since we did not observe preferential protection of myeloid over B cells, miR-24′s pro-survival effect does not explain its promotion of myelopoiesis. Moreover, expression of pro-survival protein, Bcl-xL, did not mimic miR-24′s impact on cellular differentiation, further supporting this conclusion. Our results indicate that miR-24 is a critical regulator of hematopoietic cell survival. This observation has implications for leukemogenesis. Several miRNAs that regulate apoptosis have been shown to function as either tumor suppressors or oncogenes during leukemogenesis. MiR-24 is expressed highly in primary acute myelogenous leukemia, suggesting that its pro-survival activity could contribute to the transformation of hematopoietic cells. PMID:23383180

  9. Bilateral inferior petrosal sinus sampling.

    PubMed

    Zampetti, Benedetta; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo; Loli, Paola

    2016-07-01

    Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing's syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88-100% and 67-100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50-70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. PMID:27352844

  10. Bilateral inferior petrosal sinus sampling

    PubMed Central

    Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo

    2016-01-01

    Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing’s syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88–100% and 67–100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50–70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. PMID:27352844

  11. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. PMID:27056419

  12. Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.

    PubMed

    Kuchenbauer, Florian; Mah, Sarah M; Heuser, Michael; McPherson, Andrew; Rüschmann, Jens; Rouhi, Arefeh; Berg, Tobias; Bullinger, Lars; Argiropoulos, Bob; Morin, Ryan D; Lai, David; Starczynowski, Daniel T; Karsan, Aly; Eaves, Connie J; Watahiki, Akira; Wang, Yuzhuo; Aparicio, Samuel A; Ganser, Arnold; Krauter, Jürgen; Döhner, Hartmut; Döhner, Konstanze; Marra, Marco A; Camargo, Fernando D; Palmqvist, Lars; Buske, Christian; Humphries, R Keith

    2011-09-22

    Processing of pre-miRNA through Dicer1 generates an miRNA duplex that consists of an miRNA and miRNA* strand. Despite the general view that miRNA*s have no functional role, we further investigated miRNA* species in 10 deep-sequencing libraries from mouse and human tissue. Comparisons of miRNA/miRNA* ratios across the miRNA sequence libraries revealed that 50% of the investigated miRNA duplexes exhibited a highly dominant strand. Conversely, 10% of miRNA duplexes showed a comparable expression of both strands, whereas the remaining 40% exhibited variable ratios across the examined libraries, as exemplified by miR-223/miR-223* in murine and human cell lines. Functional analyses revealed a regulatory role for miR-223* in myeloid progenitor cells, which implies an active role for both arms of the miR-223 duplex. This was further underscored by the demonstration that miR-223 and miR-223* targeted the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase axis and that high miR-223* levels were associated with increased overall survival in patients with acute myeloid leukemia. Thus, we found a supporting role for miR-223* in differentiating myeloid cells in normal and leukemic cell states. The fact that the miR-223 duplex acts through both arms extends the complexity of miRNA-directed gene regulation of this myeloid key miRNA. PMID:21628414

  13. Spontaneous alterations in left ventricular regional wall motion after acute myocardial infarction.

    PubMed

    Shen, W F; Cui, L Q; Wang, M H; Gong, L S; Lesbre, J P

    1990-12-01

    For assessing the relationship between the left ventricular (LV) wall motion abnormalities and the status of residual flow to the infarcted region, the extent of coronary artery disease and one-year outcome, 60 patients with a first transmural, Q-wave myocardial infarction (MI) underwent serial echocardiographic examinations. The abnormal wall motion (AWM) score was calculated, and the cardiac events (death, reinfarction, severe ventricular arrhythmia or congestive heart failure) after discharge were recorded. The AWM score of the infarcted area was higher in patients with total occlusion than in those with subtotal occlusion (anterior MI: 14.6 +/- 2.4 vs 7.2 +/- 2.1; inferior MI: 9.7 +/- 2.1 vs 5.1 +/-1.2, all P less than 0.01). Regional wall motion of the noninfarcted area was preserved in patients with single vessel disease but decreased in those with multivessel disease. In patients who developed cardiac events in follow-up period a higher AWM (16.4 +/- 3.7) was found than in those who did not (8.9 +/- 3.1, P less than 0.05). A score of greater than 13 had a strong prediction of cardiac events after acute MI, with a sensitivity of 81%, specificity of 94% and positive predictive accuracy of 88%. PMID:2127245

  14. miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas.

    PubMed

    Braoudaki, M; Lambrou, G I; Giannikou, K; Papadodima, S A; Lykoudi, A; Stefanaki, K; Sfakianos, G; Kolialexi, A; Tzortzatou-Stathopoulou, F; Tzetis, M; Kitsiou-Tzeli, S; Kanavakis, E

    2016-07-01

    In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma. PMID:26813564

  15. Novel Association of miR-451 with the Incidence of TEVG Stenosis in a Murine Model.

    PubMed

    Hibino, Narutoshi; Best, Cameron A; Engle, Alyson; Ghimbovschi, Svetlana; Knoblach, Susan; Nath, Dilip S; Ishibashi, Nobuyuki; Jonas, Richard A

    2016-01-01

    The development of a tissue-engineered vascular graft (TEVG) holds great promise for advancing the field of cardiac surgery. Despite the successful translation of this technology, previous reports identify the primary mode of graft failure as stenosis secondary to intimal hyperplasia. MicroRNAs (miRNAs) regulate gene expression by interfering with mRNA function and recent research has suggested miRNA as a potential therapeutic target. The role of miRNAs in TEVGs during neotissue formation is currently unknown. In this study, we investigated if miRNAs regulate the inhibition of graft stenosis. Biodegradable PGA-P(LA/CL) scaffolds were implanted as inferior vena cava interposition grafts in a murine model (n = 14). Mice were sacrificed 14 days following implantation and TEVGs were harvested for histological analysis and miRNA profiling using Affymetrix miRNA arrays. Graft diameters were measured histologically, and the largest grafts (patent group) and smallest grafts (stenosed group) were profiled (n = 4 for each group). Cell population in each graft was analyzed with immunohistochemistry using antismooth muscle actin (SMA) and antimacrophage (F4/80) antibodies. The graft diameter was significantly greater in the patent group (0.63 ± 0.06 mm) than in the stenosed group (0.17 ± 0.06 mm) (p < 0.01). Cell proliferation was significantly greater in the stenosed grafts than in patent grafts (p < 0.01: SMA [187 ± 11 vs. 77 ± 8 cells] vs. p = 0.025: F4/80 [245 ± 23 vs. 187 ± 11 cells]). MiRNA array of 1416 genes showed that in stenosed grafts, mir-451, mir-338, and mir-466 were downregulated and mir-154 was upregulated. Mir-451 exhibited the greatest difference in expression between stenosed and patent grafts by -3.1-fold. Significant negative correlation was found between the expression of mir-451 and cell proliferation (SMA: r = -0.86, p = 0.003; F4/80: r = -0.89, p = 0.001). Our data, along with previous evidence that mir-451 regulates tumor suppressor genes

  16. Measurement of the direct <mi>CP> -violating parameter <mi>Ami><mi>CP> in the decay <mi>D>+<mi>Kmi>-<mimi>+<mi>π>+

    SciTech Connect

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Borysova, M.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M. -C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Gogota, O.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kaur, M.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M. -A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Savitskyi, M.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.

    2014-12-01

    We measure the direct mi>Cmi>mi>P>-violating parameter mi>Ami>mi>Cmi>mi>Pmi> for the decay of the charged charm meson, mi>Dmi>+mi>Kmi>-mi>πmi>+mi>πmi>+ (and charge conjugate), using the full 10.4 mi>fbmi>-1 sample of mi>p>mi>p>¯ collisions at mi>smi>=1.96 mi>TeVmi> collected by the D0 detector at the Fermilab Tevatron collider. We extract the raw reconstructed charge asymmetry by fitting the invariant mass distributions for the sum and difference of charge-specific samples. This quantity is then corrected for detector-related asymmetries using data-driven methods and for possible physics asymmetries (from mi>B>mi>D

  17. MiR-1246

    PubMed Central

    Liao, Jun-Ming; Zhou, Xiang; Zhang, Yu; Lu, Hua

    2012-01-01

    Since the discovery of miRNAs, a number of miRNAs have been identified as p53’s transcriptional targets. Most of them are involved in regulation of the known p53 functions, such as cell cycle, apoptosis and senescence. Our recent study revealed miR-1246 as a novel target of p53 and its analogs p63 and p73 to suppress the expression of DYRK1A and consequently activate NFAT, both of which are associated with Down syndrome and possibly with tumorigenesis. This finding suggests that miR-1246 might serve as a likely link of the p53 family with Down syndrome. Here, we provide some prospective views on the potential role of the p53 family in Down syndrome via miR-1246 and propose a new p53-miR-1246-DYRK1A-NFAT pathway in cancer. PMID:22751441

  18. Viral miRNAs.

    PubMed

    Plaisance-Bonstaff, Karlie; Renne, Rolf

    2011-01-01

    Since 2004, more than 200 microRNAs (miRNAs) have been discovered in double-stranded DNA viruses, mainly herpesviruses and polyomaviruses (Nucleic Acids Res 32:D109-D111, 2004). miRNAs are short 22  ±  3 nt RNA molecules that posttranscriptionally regulate gene expression by binding to 3'-untranslated regions (3'UTR) of target mRNAs, thereby inducing translational silencing and/or transcript degradation (Nature 431:350-355, 2004; Cell 116:281-297, 2004). Since miRNAs require only limited complementarity for binding, miRNA targets are difficult to determine (Mol Cell 27:91-105, 2007). To date, targets have only been experimentally verified for relatively few viral miRNAs, which either target viral or host cellular gene expression: For example, SV40 and related polyomaviruses encode miRNAs which target viral large T antigen expression (Nature 435:682-686, 2005; J Virol 79:13094-13104, 2005; Virology 383:183-187, 2009; J Virol 82:9823-9828, 2008) and miRNAs of α-, β-, and γ-herpesviruses have been implicated in regulating the transition from latent to lytic gene expression, a key step in the herpesvirus life cycle. Viral miRNAs have also been shown to target various host cellular genes. Although this field is just beginning to unravel the multiple roles of viral miRNA in biology and pathogenesis, the current data strongly suggest that virally encoded miRNAs are able to regulate fundamental biological processes such as immune recognition, promotion of cell survival, angiogenesis, proliferation, and cell differentiation. This chapter aims to summarize our current knowledge of viral miRNAs, their targets and function, and the challenges lying ahead to decipher their role in viral biology, pathogenesis, and for γ-herepsvirus-encoded miRNAs, potentially tumorigenesis. PMID:21431678

  19. Inferior Vena Cava Filter Placement during Pregnancy: An Adjuvant Option When Medical Therapy Fails

    PubMed Central

    Serrano, Fátima; Torres, Rita; Borges, Augusta

    2013-01-01

    The authors present a case of a 27-year-old multiparous woman, with multiple thrombophilia, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter. At 15th week of gestation, following an acute deep venous thrombosis of the right inferior limb, anticoagulant therapy with low-molecular-weight heparin (LMWH) was instituted without improvement in her clinical status. Subsequently, at 18 weeks of pregnancy, LMWH was switched to warfarin. At 30th week of gestation, the maintenance of high thrombotic risk was the premise for placement of an inferior vena cava filter for prophylaxis of pulmonary embolism during childbirth and postpartum. There were no complications and a vaginal delivery was accomplished at 37 weeks of gestation. Venal placement of inferior vena cava filters is an attractive option as prophylaxis for pulmonary embolism during pregnancy. PMID:23781361

  20. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  1. [Inferior alveolar nerve repositioning in implant surgery].

    PubMed

    Ardekian, L; Salnea, J; Abu el-Naaj, I; Gutmacher, T; Peled, M

    2001-04-01

    Severe resorption of the posterior mandible possesses one of the most difficult restorative challenges to the implant surgery today. This resorption may prevent the placement of dental implants without the potentially damage to the inferior alveolar nerve. To create the opportunity of insertion dental implants of adequately length in those cases, the technique of nerve repositioning has been advocated. The purpose of this article is to describe two cases of nerve repositioning combined with placement of dental implants. Both cases showed appropriate postoperative healing without damage to the inferior alveolar nerve. The inferior alveolar nerve repositioning technique seems to be an acceptable alternative to augmentation procedure prior to dental implants placement in cases exhibiting atrophic posterior mandibular ridges. PMID:11494807

  2. Tensile properties of the inferior glenohumeral ligament.

    PubMed

    Bigliani, L U; Pollock, R G; Soslowsky, L J; Flatow, E L; Pawluk, R J; Mow, V C

    1992-03-01

    The tensile properties of the inferior glenohumeral ligament have been determined in 16 freshly frozen cadaver shoulders. The inferior glenohumeral ligament was divided into three anatomical regions: a superior band, an anterior axillary pouch, and a posterior axillary pouch. This yielded 48 bone-ligament-bone specimens, which were tested to failure in uniaxial tension. The superior band was consistently the thickest region, averaging 2.79 mm. The thickness of the inferior glenohumeral ligament decreased from antero-superiorly to postero-inferiorly. The resting length of all three anatomical regions was not statistically different. Total specimen strain to failure for all bone-ligament-bone specimens averaged 27%. Variations occurred between the three regions, with the anterior pouch specimens failing at a higher strain (34%) than those from the superior band (24%) or the posterior pouch (23%). Strain to failure for the ligament midsubstance (11%) was found to be significantly less than that for the entire specimen (27%). Thus, larger strain must occur near the insertion sites of the inferior glenohumeral ligament. Stress at failure was found to be nearly identical for the three regions of the ligament, averaging 5.5 MPa. These values are lower than those reported for other soft tissues, such as the anterior cruciate ligament and patellar tendon. The anterior pouch was found to be less stiff than the other two regions, perhaps suggesting that it is composed of more highly crimped collagen fibers. Three failure sites were seen for the inferior glenohumeral ligament: the glenoid insertion (40%), the ligament substance (35%), and the humeral insertion (25%). In addition, significant capsular stretching occurred before failure, regardless of the failure mode. PMID:1740736

  3. Anatomy of Inferior Mesenteric Artery in Fetuses

    PubMed Central

    Nuzhat, Ayesha

    2016-01-01

    Aim. To analyze Inferior Mesenteric Artery in fetuses through its site of origin, length, diameter, and variation of its branches. Method. 100 fetuses were collected from various hospitals in Warangal at Kakatiya Medical College in Andhra Pradesh, India, and were divided into two groups, group I (second-trimester fetuses) and group II (third-trimester fetuses), followed by dissection. Result. (1) Site of Origin. In group I fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra in 33 out of 34 fetuses (97.2%). In one fetus it was at first lumbar vertebra, 2.8%. In all group II fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra. (2) Length. In group I fetuses it ranged between 18 and 30 mm, average being 24 mm except in one fetus where it was 48 mm. In group II fetuses the length ranged from 30 to 34 mm, average being 32 mm. (3) Diameter. In group I fetuses it ranged from 0.5 to 1 mm, and in group II fetuses it ranged from 1 to 2 mm, average being 1.5 mm. (4) Branches. Out of 34 fetuses of group I, 4 fetuses showed variation. In one fetus left colic artery was arising from abdominal aorta, 2.9%. In 3 fetuses, Inferior Mesenteric Artery was giving a branch to left kidney, 8.8%. Out of 66 fetuses in group II, 64 had normal branching. In one fetus left renal artery was arising from Inferior Mesenteric Artery, 1.5%, and in another fetus one accessory renal artery was arising from Inferior Mesenteric Artery and entering the lower pole of left kidney. Conclusion. Formation, course, and branching pattern of an artery depend on development and origin of organs to attain the actual adult position. PMID:27313956

  4. Anatomy of Inferior Mesenteric Artery in Fetuses.

    PubMed

    Nuzhat, Ayesha

    2016-01-01

    Aim. To analyze Inferior Mesenteric Artery in fetuses through its site of origin, length, diameter, and variation of its branches. Method. 100 fetuses were collected from various hospitals in Warangal at Kakatiya Medical College in Andhra Pradesh, India, and were divided into two groups, group I (second-trimester fetuses) and group II (third-trimester fetuses), followed by dissection. Result. (1) Site of Origin. In group I fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra in 33 out of 34 fetuses (97.2%). In one fetus it was at first lumbar vertebra, 2.8%. In all group II fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra. (2) Length. In group I fetuses it ranged between 18 and 30 mm, average being 24 mm except in one fetus where it was 48 mm. In group II fetuses the length ranged from 30 to 34 mm, average being 32 mm. (3) Diameter. In group I fetuses it ranged from 0.5 to 1 mm, and in group II fetuses it ranged from 1 to 2 mm, average being 1.5 mm. (4) Branches. Out of 34 fetuses of group I, 4 fetuses showed variation. In one fetus left colic artery was arising from abdominal aorta, 2.9%. In 3 fetuses, Inferior Mesenteric Artery was giving a branch to left kidney, 8.8%. Out of 66 fetuses in group II, 64 had normal branching. In one fetus left renal artery was arising from Inferior Mesenteric Artery, 1.5%, and in another fetus one accessory renal artery was arising from Inferior Mesenteric Artery and entering the lower pole of left kidney. Conclusion. Formation, course, and branching pattern of an artery depend on development and origin of organs to attain the actual adult position. PMID:27313956

  5. Improving the ECG classification of inferior and lateral myocardial infarction by inversion of lead aVR

    PubMed Central

    Menown, I; Adgey, A

    2000-01-01

    OBJECTIVE—To assess whether the use of inverted lead aVR (−aVR) would improve the classification of acute inferior or lateral myocardial infarction presenting with ST elevation.
DESIGN—Observational study. The presence of ⩾ 1 mm ST elevation in lead −aVR (derived by manual assessment of ST depression in conventional lead aVR) was determined by a single investigator, blinded to patient outcome.
PATIENTS—173 consecutive patients with chest pain for ⩽ 12 hours and ST elevation of ⩾ 1 mm in inferior leads (II, III, aVF) or lateral leads (I, aVL, V5, V6), excluding those with anterolateral ST elevation.
MAIN OUTCOME MEASURE—Incidence of ST elevation in lead −aVR in patients with inferior or lateral ST elevation, or both.
RESULTS—ST elevation in lead −aVR was present in 25 of 136 patients (18%) with inferior but no lateral ST elevation (indicating greater superior involvement) and in three of 11 patients (27%) with lateral but no inferior ST elevation (indicating greater inferior involvement). ST elevation in lead −aVR bridged the gap between inferior and lateral ST elevation in 15 of 25 (60%) patients with inferior and lateral chest lead (V5/V6) ST elevation, and in all patients with inferior and lateral limb lead (I/aVL) ST elevation. The presence of ST elevation in lead −aVR was associated with a larger infarct size as defined by median peak creatine kinase on serial sampling: 1780 v 987  mmol/l; p = 0.021.
CONCLUSIONS—Use of lead −aVR improves the ECG classification of acute inferior or lateral acute myocardial infarction and thus may be useful as part of the routine 12 lead ECG assessment of such patients.


Keywords: electrocardiography; acute myocardial infarction PMID:10814623

  6. Cholelithiasis demonstrated on hepatobiliary scintigraphy as a photopenic defect within the inferior portion of the liver

    SciTech Connect

    Moreno, A.J.; Yedinak, M.A.; Turnbull, G.L.; Spicer, M.J.; Brown, T.J.

    1984-11-01

    A 47-year-old man presented with the clinical findings of acute cholecystitis. During hepatobiliary scintigraphy using Tc-99m DISIDA, a persistent photopenic defect was noted within the inferior portion of the liver in the region of the gallbladder. Abdominal ultrasonography revealed large gallstones with acoustic shadowing within a normal-sized gallbladder. Eleven large gallstones were found within a normal-sized intrahepatic gallbladder at surgery.

  7. NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

    PubMed Central

    Shah, N M; Zaitseva, L; Bowles, K M; MacEwan, D J; Rushworth, S A

    2015-01-01

    Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics. PMID:25323587

  8. Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection: is early surgical exploration warranted?

    PubMed

    Alexiades, Nikita G; Ellis, Jason A; Meyers, Philip M; Connolly, E Sander

    2016-06-01

    The natural history of spontaneous cerebral artery dissection and thrombosis remains uncertain. Concurrent subarachnoid hemorrhage further complicates the therapeutic approach. Thus the best strategy for managing patients with acute vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we present a case of spontaneous posterior inferior cerebellar artery dissection presenting with subarachnoid hemorrhage and acute thrombosis. Although the patient was initially managed conservatively, angiographic follow-up demonstrated recanalization of the diseased vessel, necessitating definitive treatment. Thus we propose that angiographic follow-up is necessary in the management of patients with subarachnoid hemorrhage in association with apparent vessel thrombosis. PMID:25987592

  9. The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice

    PubMed Central

    Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Hua, Xiang; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Xiong, Wei; Wysoczynski, Marcin; Sithu, Srinivas D.; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

    2015-01-01

    MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumor necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis, and miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway and could be a therapeutic target for preventing pathologic necrosis. PMID:25990308

  10. Multidirectional Instability Accompanying an Inferior Labral Cyst

    PubMed Central

    Ji, Jong-Hun; Kim, Sung-Jae

    2010-01-01

    Paralabral cyst of the shoulder joint can be observed in 2% to 4% of the general population, particularly in men during the third and fourth decade. On average, these cysts measure 10 mm to 20 mm in diameter and are located preferentially on the postero-superior aspect of the glenoid. The MRI has increased the frequency of the diagnosis of paralabral cysts of the shoulder joint. Paralabral cysts of the shoulder joint usually develop in the proximity of the labrum. The relationship between shoulder instability and labral tears is well known, however, the association of shoulder instability with a paralabral cyst is rare. Shoulder instability may cause labral injury or labral injury may cause shoulder instability, and then injured tear develops paralabral cyst. In our patient, the inferior paralabral cyst may be associated with inferior labral tears and instability MRI. PMID:20514270

  11. A novel technique for inferior rectus recession

    PubMed Central

    Gokyigit, Birsen; Akar, Serpil; Yilmaz, Omer Faruk

    2014-01-01

    Purpose To introduce a novel technique of inferior rectus recession operation to allow larger amounts of recession without causing lower lid retraction and to compare this method with the results obtained in standard inferior rectus recession. Material and methods This study included 20 patients operated on in the authors’ clinic. The median age of the patients was 24.5±18.6 (4–73) years and the median follow-up was 9.3±11.8 (3–43) months. Ten patients operated on with the standard method were labeled Group 1 and ten patients operated on with the new method were labeled Group 2. Without exceeding 4 mm, inferior rectus recession to the whole muscle was performed in Group 1 patients. Inferior rectus recession was also performed on patients in Group 2 following the new method. Using a spatula, approximately 10% of the muscle surface fibers were detached intact as a thin layer, and the remaining 90% of deeper fibers were recessed 4–8 mm as planned. Patients’ preoperative deviations and lower lid positions were recorded. The same parameters were checked in the first and third month postoperatively. Both groups were evaluated retrospectively by screening their files, and the Mann–Whitney U test was used for statistical evaluation. Results Lower lid retraction was seen in four patients of Group 1. There was no retraction in Group 2. While there was a need to perform additional vertical muscle procedures for vertical deviations and lower lid retractions in Group 1, it was observed that there was no need for additional procedures in Group 2 patients. There was a statistically meaningful difference between the two procedures (P<0.05). Conclusion This novel technique was found to be an effective surgical method for permitting more recession without the risk of lower lid retraction. PMID:24492531

  12. Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

    PubMed Central

    Sondermeijer, Brigitte M.; Bakker, Annemieke; Halliani, Amalia; de Ronde, Maurice W. J.; Marquart, Arnoud A.; Tijsen, Anke J.; Mulders, Ties A.; Kok, Maayke G. M.; Battjes, Suzanne; Maiwald, Steffi; Sivapalaratnam, Suthesh; Trip, Mieke D.; Moerland, Perry D.; Meijers, Joost C. M.; Creemers, Esther E.; Pinto-Sietsma, Sara-Joan

    2011-01-01

    Background Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. Methodology/Principal Findings In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Conclusion/Significance Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study. PMID:22022480

  13. Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

    NASA Technical Reports Server (NTRS)

    Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

    2003-01-01

    Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

  14. Recent advances in the diagnosis and treatment of acute myocardial infarction

    PubMed Central

    Reddy, Koushik; Khaliq, Asma; Henning, Robert J

    2015-01-01

    The Third Universal Definition of Myocardial Infarction (MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient’s plasma of cardiac troponin (cTn) with at least one cTn measurement greater than the 99th percentile of the upper normal reference limit during: (1) symptoms of myocardial ischemia; (2) new significant electrocardiogram (ECG) ST-segment/T-wave changes or left bundle branch block; (3) the development of pathological ECG Q waves; (4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or (5) identification of intracoronary thrombus by angiography or autopsy. Myocardial infarction, when diagnosed, is now classified into five types. Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI. However, high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis. The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated, especially if the initial ECG is not diagnostic of MI. There have been significant advances in adjunctive pharmacotherapy, procedural techniques and stent technology in the treatment of patients with MIs. The routine use of antiplatelet agents such as clopidogrel, prasugrel or ticagrelor, in addition to aspirin, reduces patient morbidity and mortality. Percutaneous coronary intervention (PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI. Drug eluting coronary stents are safe and beneficial with primary coronary intervention. Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein IIb/IIIa receptor antagonists and is associated with a significant reduction in bleeding. The intra-coronary use of a glycoprotein IIb/IIIa antagonist can reduce infarct size. Pre- and post-conditioning techniques can provide additional cardioprotection. However, the incidence and

  15. Recent advances in the diagnosis and treatment of acute myocardial infarction.

    PubMed

    Reddy, Koushik; Khaliq, Asma; Henning, Robert J

    2015-05-26

    The Third Universal Definition of Myocardial Infarction (MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin (cTn) with at least one cTn measurement greater than the 99(th) percentile of the upper normal reference limit during: (1) symptoms of myocardial ischemia; (2) new significant electrocardiogram (ECG) ST-segment/T-wave changes or left bundle branch block; (3) the development of pathological ECG Q waves; (4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or (5) identification of intracoronary thrombus by angiography or autopsy. Myocardial infarction, when diagnosed, is now classified into five types. Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI. However, high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis. The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated, especially if the initial ECG is not diagnostic of MI. There have been significant advances in adjunctive pharmacotherapy, procedural techniques and stent technology in the treatment of patients with MIs. The routine use of antiplatelet agents such as clopidogrel, prasugrel or ticagrelor, in addition to aspirin, reduces patient morbidity and mortality. Percutaneous coronary intervention (PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI. Drug eluting coronary stents are safe and beneficial with primary coronary intervention. Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein IIb/IIIa receptor antagonists and is associated with a significant reduction in bleeding. The intra-coronary use of a glycoprotein IIb/IIIa antagonist can reduce infarct size. Pre- and post-conditioning techniques can provide additional cardioprotection. However, the incidence and

  16. A follow-up study of cognitive impairment due to inferior capsular genu infarction.

    PubMed

    Madureira, S; Guerreiro, M; Ferro, J M

    1999-09-01

    Abulia, memory loss, other cognitive deficits, and behavioral changes consistent with dementia can follow an inferior capsular genu infarction, but only little is known about the time course of these disturbances. The present study describes the long-term outcome of cognitive defects in four patients with inferior capsular genu infarction who underwent a neuropsychological examination within 3 and 12 months of onset. Three patients had infarcts in the inferior genu of the left internal capsule and had similar symptoms in the acute phase: disorientation, memory loss, language impairment, and behavioral changes. The patient with right-side infarct showed memory impairment and behavioral changes. Three patients had deficits in one or more cognitive domains on the first assessment, but none was demented. By the second evaluation all subjects had improved. In two patients there were a moderate memory defect persisted and a language disturbance. Improvement in these disturbances during long-time follow-up demonstrates that there are alternative pathways that reestablish the functional connections damaged by the strategically located capsular genu infarct. Inferior capsular genu infarction is not a cause of persisting "strategic infarct dementia." PMID:10525972

  17. miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.

    PubMed

    Lechman, Eric R; Gentner, Bernhard; Ng, Stanley W K; Schoof, Erwin M; van Galen, Peter; Kennedy, James A; Nucera, Silvia; Ciceri, Fabio; Kaufmann, Kerstin B; Takayama, Naoya; Dobson, Stephanie M; Trotman-Grant, Aaron; Krivdova, Gabriela; Elzinga, Janneke; Mitchell, Amanda; Nilsson, Björn; Hermans, Karin G; Eppert, Kolja; Marke, Rene; Isserlin, Ruth; Voisin, Veronique; Bader, Gary D; Zandstra, Peter W; Golub, Todd R; Ebert, Benjamin L; Lu, Jun; Minden, Mark; Wang, Jean C Y; Naldini, Luigi; Dick, John E

    2016-02-01

    To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance. PMID:26832662

  18. miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

    PubMed Central

    Lechman, Eric R.; Gentner, Bernhard; Ng, Stanley W.K.; Schoof, Erwin M.; van Galen, Peter; Kennedy, James A.; Nucera, Silvia; Ciceri, Fabio; Kaufmann, Kerstin B.; Takayama, Naoya; Dobson, Stephanie M.; Trotman-Grant, Aaron; Krivdova, Gabriela; Elzinga, Janneke; Mitchell, Amanda; Nilsson, Björn; Hermans, Karin G.; Eppert, Kolja; Marke, Rene; Isserlin, Ruth; Voisin, Veronique; Bader, Gary D.; Zandstra, Peter W.; Golub, Todd R.; Ebert, Benjamin L.; Lu, Jun; Minden, Mark; Wang, Jean C.Y.; Naldini, Luigi; Dick, John E.

    2016-01-01

    Summary To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance. PMID:26832662

  19. [Experimental subendocardial postero-inferior infarctions].

    PubMed

    Medrano, G A; de Micheli, A

    1990-01-01

    In 30 mongrel dog hearts, epicardial and thoracic unipolar records were obtained after myocardial damage was produced by infiltration of 96% alcohol in the postero-inferior free left ventricular wall. Necrosis was transmural in 5 cases, subendocardial in 11 and intramural in 10. In 4 dogs, intramural unipolar and bipolar leads were recorded in order to determine the electrical subendocardium and its relation to potentials of Purkinje's fibres. At the end of each experiment, left posterior subdivision block (LPSB) was provoked. In 90% of the cases, direct epicardial records were QS in transmural infarction, qrS or less frequently QRS in subendocardial ones, and rS or qRS in the presence of intramural necrosis. In several cases myocardial necrosis was located in the middle third instead of the inferior third, but the direct registries were similar. Nevertheless the surface leads (II, III and aVF) did not show abnormal Q waves or greater voltage of Q and S, but there were RS complexes in V1 and V2. In 80% of the cases, transmural necrosis of inferior third was manifested by QS complexes and subendocardial necrosis by rS or qRS complexes with increased Q and S waves and reduced R waves. LPSB masked the signs of necrosis. There is no justification for speaking of myocardial infarction with or without abnormal Q waves, because it does not add more precision. Moreover these expressions can create confusion in cases of middle or high posterior myocardial necrosis, revealed by RS complexes in V1 and V2. PMID:2268169

  20. Hydroxytyrosol supplementation modulates the expression of miRNAs in rodents and in humans.

    PubMed

    Tomé-Carneiro, Joao; Crespo, María Carmen; Iglesias-Gutierrez, Eduardo; Martín, Roberto; Gil-Zamorano, Judit; Tomas-Zapico, Cristina; Burgos-Ramos, Emma; Correa, Carlos; Gómez-Coronado, Diego; Lasunción, Miguel A; Herrera, Emilio; Visioli, Francesco; Dávalos, Alberto

    2016-08-01

    Dietary microRNAs (miRNAs) modulation could be important for health and wellbeing. Part of the healthful activities of polyphenols might be due to a modulation of miRNAs' expression. Among the most biologically active polyphenols, hydroxytyrosol (HT) has never been studied for its actions on miRNAs. We investigated whether HT could modulate the expression of miRNAs in vivo. We performed an unbiased intestinal miRNA screening in mice supplemented (for 8 weeks) with nutritionally relevant amounts of HT. HT modulated the expression of several miRNAs. Analysis of other tissues revealed consistent HT-induced modulation of only few miRNAs. Also, HT administration increased triglycerides levels. Acute treatment with HT and in vitro experiments provided mechanistic insights. The HT-induced expression of one miRNA was confirmed in healthy volunteers supplemented with HT in a randomized, double-blind and placebo-controlled trial. HT consumption affects specific miRNAs' expression in rodents and humans. Our findings suggest that the modulation of miRNAs' action through HT consumption might partially explain its healthful activities and might be pharmanutritionally exploited in current therapies targeting endogenous miRNAs. However, the effects of HT on triglycerides warrant further investigations. PMID:27322812

  1. Potential microRNA biomarkers for acute ischemic stroke.

    PubMed

    Zeng, Ye; Liu, Jing-Xia; Yan, Zhi-Ping; Yao, Xing-Hong; Liu, Xiao-Heng

    2015-12-01

    Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT‑qPCR). Four confirmed differentially expressed miRNAs (miR‑9, ‑22, ‑23 and ‑125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR‑9, ‑30, ‑33, ‑124, ‑181, ‑218 and ‑330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA‑targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA‑targeted genes identified serve as potential therapeutic targets for acute ischemic stroke. PMID:26459744

  2. miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease

    PubMed Central

    Appelbaum, Sebastian; Karakas, Mahir; Ojeda, Francisco; Lau, Denise M.; Hartmann, Tim; Lackner, Karl J.; Westermann, Dirk; Schnabel, Renate B.; Blankenberg, Stefan; Zeller, Tanja

    2015-01-01

    Background Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction. Objectives The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD. Methods Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR). Results The median follow-up period was 4 years (IQR 2.78–5.04). The median age of all patients was 64 years (IQR 57–69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89). Conclusion Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers

  3. MI1ANAV

    Atmospheric Science Data Center

    2014-09-03

    MI1ANAV MISR Level 1A Navigation Data: Reformatted Annotated Level 1A Product for the Navigation Data, which contains samples of the Terra Platform position and ... Specification Versioning History:  Engineering, Navigation SCAR-B Block:  SCAR-B ...

  4. MI1AENG1

    Atmospheric Science Data Center

    2014-09-03

    MI1AENG1 MISR Level 1A Engineering Data File Type 1: Reformatted Annotated Level 1A product for the camera engineering data, which represents indicators of sampled measurements. ... Status Production Report Read Software Files :  Data Product Specification Versioning ...

  5. MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation.

    PubMed

    Chen, Yongxin; Melton, David W; Gelfond, Jonathan A L; McManus, Linda M; Shireman, Paula K

    2012-11-01

    MicroRNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. PMID:22968638

  6. MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation

    PubMed Central

    Chen, Yongxin; Melton, David W.; Gelfond, Jonathan A. L.; McManus, Linda M.

    2012-01-01

    MicroRNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. PMID:22968638

  7. Transvenous embolization of a dural carotid-cavernous sinus fistula via the inferior ophthalmic vein.

    PubMed

    Michels, Kevin S; Ng, John D; Falardeau, Julie; Roberts, Warren G; Petersen, Bryan; Nesbit, Gary M; Barnwell, Stanley L

    2007-01-01

    A 76-year-old woman presented with an acute onset of right periocular pain, diplopia, ocular injection, progressive proptosis, and periocular swelling. She had an unremarkable past medical history, and the erythrocyte sedimentation rate and complete blood count were normal. A carotid-cavernous sinus fistula was suspected, and an MRI demonstrated enlargement of the superior ophthalmic vein posterior to the globe and enlargement of the inferior ophthalmic vein throughout its entire course. Cerebral arteriography demonstrated a dural cavernous sinus fistula. The inferior ophthalmic vein was accessed via the inferonasal orbital space and was catheterized for delivery of multiple platinum coils to the cavernous sinus fistula. Follow-up venograms demonstrated occlusion of the fistula. At 2-month follow-up, there was a residual sixth nerve palsy and resolution of symptoms, including proptosis and periocular swelling. PMID:18030122

  8. Anatomic Variant of Liver, Gall Bladder and Inferior Vena Cava

    PubMed Central

    Gladwin, V.; Chand, Parkash

    2016-01-01

    The morphology and relations of liver, gall bladder and inferior vena cava are cardinal. Their anatomical variations may be a reason for the adverse surgical outcome. During routine anatomy dissection of an abdomen, we noticed a variant liver, gall bladder and inferior vena cava in a 63-year-old male cadaver. In the specimen, a retrohepatic segment of inferior vena cava was found to be intrahepatic. On dissection, it was observed that inferior vena cava was covered entirely by a liver tissue on its dorsal aspect. In the same specimen, the gall bladder had undulated inferior surface. On dissection of the gall bladder, numerous mucosal folds were present in the interior. A band of fibrous tissue was found, which was extending from the right side of the gall bladder to the falciform ligament. Hence, preoperative scanning of congenital variations of the liver, gall bladder and inferior vena cava may be compassionate in planning safe surgeries and interventional abdominal procedures.

  9. miRTargetLink—miRNAs, Genes and Interaction Networks

    PubMed Central

    Hamberg, Maarten; Backes, Christina; Fehlmann, Tobias; Hart, Martin; Meder, Benjamin; Meese, Eckart; Keller, Andreas

    2016-01-01

    Information on miRNA targeting genes is growing rapidly. For high-throughput experiments, but also for targeted analyses of few genes or miRNAs, easy analysis with concise representation of results facilitates the work of life scientists. We developed miRTargetLink, a tool for automating respective analysis procedures that are frequently applied. Input of the web-based solution is either a single gene or single miRNA, but also sets of genes or miRNAs, can be entered. Validated and predicted targets are extracted from databases and an interaction network is presented. Users can select whether predicted targets, experimentally validated targets with strong or weak evidence, or combinations of those are considered. Central genes or miRNAs are highlighted and users can navigate through the network interactively. To discover the most relevant biochemical processes influenced by the target network, gene set analysis and miRNA set analysis are integrated. As a showcase for miRTargetLink, we analyze targets of five cardiac miRNAs. miRTargetLink is freely available without restrictions at www.ccb.uni-saarland.de/mirtargetlink. PMID:27089332

  10. Injuries of the inferior vena cava.

    PubMed

    Burch, J M; Feliciano, D V; Mattox, K L; Edelman, M

    1988-12-01

    Beginning in 1946, 577 patients with inferior vena cava injuries were managed at a single institution. After decreasing from 37 to 30 percent, the mortality rate showed a distinct increase in the last 7 years studied. This increase was related to an increasing percentage of patients who arrived in the emergency center in severe shock and required resuscitative thoracotomy. In-hospital care advances have not kept pace with improvements in prehospital care. Although venous complications have not been infrequent, morbidity has not been a significant long-term problem. Fatal pulmonary embolism occurred and was a special problem for patients over the age of 50. More basic research is needed to expedite diagnosis and vascular control in addition to understanding and treating the severe metabolic problems of patients dying from shock and hemorrhage. PMID:3202271

  11. Bilateral inferior petrosal sinus sampling using vasopressin

    PubMed Central

    Kotwal, Narendra; Kumar, Yogesh; Upreti, Vimal; Singh, Amandeep; Garg, M. K.

    2016-01-01

    Context: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS) is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH) improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. Aims: To study the tumor localization and lateralization in difficult to localize cases of ACTH-dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. Settings and Design: Prospective observational study. Subjects and Methods: Six patients (5 females) meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. Results: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. Conclusions: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS. PMID:27186561

  12. miR-9 is a tumor suppressor in pediatric AML with t(8;21).

    PubMed

    Emmrich, S; Katsman-Kuipers, J E; Henke, K; Khatib, M E; Jammal, R; Engeland, F; Dasci, F; Zwaan, C M; den Boer, M L; Verboon, L; Stary, J; Baruchel, A; de Haas, V; Danen-van Oorschot, A A; Fornerod, M; Pieters, R; Reinhardt, D; Klusmann, J H; van den Heuvel-Eibrink, M M

    2014-05-01

    MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of acute myeloid leukemia (AML) with t(8;21), inv(16) or mixed lineage leukemia (MLL) rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor-suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor-suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. PMID:24270738

  13. Kounis syndrome: inferior ST-segment elevation myocardial infarction following a bumblebee sting.

    PubMed

    Zanini, Gregoriana; Fontanella, Benedetta; Racheli, Marco; Bortolotti, Monica; Pasini, Gian Franco

    2013-08-01

    The Kounis syndrome was first described in 1991 as'the allergic angina syndrome'which could progress to acute myocardial infarction which was named'allergic myocardial infarction. There are several causes underlying this syndrome including drugs, various conditions and a variety of environmental exposure factors such as animal stings. Hymenoptera stings can induce Kounis syndrome because hymenoptera venom contains allergenic proteins and peptides. The following case report describes a patient who experienced an anaphylactic shock associated with coronary artery ischaemia (inferior ST-segment elevation myocardial infarction) after a bumblebee sting. PMID:24187772

  14. Reconstructive endovascular treatment of ruptured vertebral artery dissection involving the posterior inferior cerebellar artery.

    PubMed

    Ota, Takahiro; Sato, Masayuki; Amano, Tatsuo; Saito, Akira; Matsumaru, Yuji

    2016-06-01

    Two cases with ruptured vertebral artery (VA) dissection involving the origin of the posterior inferior cerebellar artery (PICA) are presented. Endovascular proximal occlusion of the dissected segment proximal to the PICA origin was performed, leaving the PICA patent in the acute stage. Stent placement from the PICA to the VA through the contralateral VA and coil embolization were added to the residual dissection in the chronic stage. Rebleedings were not observed. This is the first report of a staged, combined strategy for the treatment of a ruptured PICA involving VA dissection, which enabled preservation of the PICA without bypass surgery. PMID:27038168

  15. Varices of inferior epigastric veins caused by chronic inferior vena cava obstruction: mimicking normal venous flow pattern on radionuclide venography.

    PubMed

    Karacalioglu, Ozgur; Sonmez, Alper; Ilgan, Seyfettin; Soylu, Kenan; Emer, Ozdes; Ozguven, Mehmet

    2005-05-01

    A 21-year-old patient with long-standing inferior vena cava obstruction secondary to idiopathic thrombosis extending from the external iliac veins underwent a radionuclide venography with Tc-99m pertechnetate labeled erythrocytes. The blood pool phase of the study revealed bilaterally distorted inferior epigastric veins mimicking normal venous flow pattern. The authors present this case to discuss the possible alternative routes and the underlying physiopathologic mechanism of this unusual flow pattern in chronic inferior vena cava obstruction. PMID:15981678

  16. MicroRNAs: Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome

    PubMed Central

    CAO, YONGMEI; LYU, YI; TANG, JIAHUA; LI, YINGCHUAN

    2016-01-01

    Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are common and complex inflammatory lung diseases. MicroRNAs (miRNAs), a type of non-coding RNA molecule that regulate gene expression at the post-transcriptional level, have emerged as a novel class of gene regulators, which have critical roles in a wide range of human disorders and diseases, including ALI. Certain types of miRNAs are abnormally expressed in response to lung injury. miRNAs can regulate inflammation pathways by targeting specific molecules and modulate immune response in the process of lung injury and repair. The regulation of miRNA can relieve injury response and promote the recovery of ALI/ARDS. Therefore, miRNAs may serve as novel therapeutic targets in ALI/ARDS. PMID:27123242

  17. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise.

    PubMed

    Van Craenenbroeck, Amaryllis H; Ledeganck, Kristien J; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y; Verpooten, Gert A; Vrints, Christiaan J; Couttenye, Marie M; Van Craenenbroeck, Emeline M

    2015-12-15

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD. PMID:26475583

  18. Anterior Inferior Iliac Spine Avulsion Fracture

    PubMed Central

    Serbest, Sancar; Tosun, Hacı Bayram; Tiftikçi, Uğur; Oktas, Birhan; Kesgin, Engin

    2015-01-01

    Abstract Avulsion fractures of the pelvic apophyses rarely occur in adolescent athletes in the course of sudden strong contraction of muscle attached to growth cartilage. This injury may usually be misdiagnosed for tendon or muscle strain. Patient's history, physical examination, and radiologic studies are important for diagnosis. The literature includes only a few case reports but no case series as yet. The aim of this study was to present the results of 5 cases of anterior inferior iliac spine (AIIS) avulsion fractures treated conservatively. The study included 5 patients (4 male, 1 female, mean age 13.6 years) who underwent conservative treatment for AIIS avulsion fractures and had an adequate follow-up. All patients were admitted to the emergency department and misdiagnosed as muscle strain. Three of them were football player, 1 skier, and 1 fighter. Each patient was treated with immobilization and nonsteroidal anti-inflammatory drugs. At follow-up, all patients showed relief from their pain and mechanical symptoms and regained full range of motion and returned to their previous levels of activity. Diagnosis requires careful attention to the physical examination and imaging. In this series, all pelvic avulsion fractures (100%) were managed successfully with a conservative approach. Good results and return to previous levels of activity can be achieved with conservative treatment. PMID:25700329

  19. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe

  20. Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study

    PubMed Central

    Politano, Gianfranco; Inghilleri, Simona; Morbini, Patrizia; Calabrese, Fiorella; Benso, Alfredo; Savino, Alessandro; Cova, Emanuela; Zampieri, Davide; Meloni, Federica

    2016-01-01

    The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs–miR-34a and miR-21 –was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline. PMID:27564214

  1. Shoot bending promotes flower bud formation by miRNA-mediated regulation in apple (Malus domestica Borkh.).

    PubMed

    Xing, Libo; Zhang, Dong; Zhao, Caiping; Li, Youmei; Ma, Juanjuan; An, Na; Han, Mingyu

    2016-02-01

    Flower induction in apple (Malus domestica Borkh.) trees plays an important life cycle role, but young trees produce fewer and inferior quality flower buds. Therefore, shoot bending has become an important cultural practice, significantly promoting the capacity to develop more flower buds during the growing seasons. Additionally, microRNAs (miRNAs) play essential roles in plant growth, flower induction and stress responses. In this study, we identified miRNAs potentially involved in the regulation of bud growth, and flower induction and development, as well as in the response to shoot bending. Of the 195 miRNAs identified, 137 were novel miRNAs. The miRNA expression profiles revealed that the expression levels of 68 and 27 known miRNAs were down-regulated and up-regulated, respectively, in response to shoot bending, and that the 31 differentially expressed novel miRNAs between them formed five major clusters. Additionally, a complex regulatory network associated with auxin, cytokinin, abscisic acid (ABA) and gibberellic acid (GA) plays important roles in cell division, bud growth and flower induction, in which related miRNAs and targets mediated regulation. Among them, miR396, 160, 393, and their targets associated with AUX, miR159, 319, 164, and their targets associated with ABA and GA, and flowering-related miRNAs and genes, regulate bud growth and flower bud formation in response to shoot bending. Meanwhile, the flowering genes had significantly higher expression levels during shoot bending, suggesting that they are involved in this regulatory process. This study provides a framework for the future analysis of miRNAs associated with multiple hormones and their roles in the regulation of bud growth, and flower induction and formation in response to shoot bending in apple trees. PMID:26133232

  2. Sleep Apnea Prevalence in Acute Myocardial Infarction - the Sleep Apnea in Post Acute Myocardial Infarction Patients (SAPAMI) Study

    PubMed Central

    Ludka, Ondrej; Stepanova, Radka; Vyskocilova, Martina; Galkova, Lujza; Mikolaskova, Monika; Belehrad, Milos; Kostalova, Jana; Mihalova, Zuzana; Drozdova, Adela; Hlasensky, Jiri; Gacik, Michal; Pudilova, Lucie; Mikusova, Tereza; Fischerova, Blanka; Sert-Kuniyoshi, Fatima; Kara, Tomas; Spinar, Jindrich; Somers, Virend K.

    2014-01-01

    Background While sleep apnea (SA) might be a modifiable cardiovascular risk factor, recent data suggest that SA is severely underdiagnosed in patients after acute myocardial infarction (MI). There is limited evidence about day-night variation of onset of MI on dependence of having SA. We therefore investigated the prevalence of SA and examined the day-night variation of onset of MI in acute MI patients. Methods We prospectively studied 782 consecutive patients admitted to the hospital with the diagnosis of acute MI. All subjects underwent sleep evaluations using a portable device after at least 48 hours post-admission. Using the apnea-hypopnea index (AHI), groups were defined as patients without SA (<5 events/hour), mild SA (5–15 events/hour), moderate SA (15–30 events/hour), and severe SA (≥30 events/hour). Results Almost all patients (98%) underwent urgent coronary angiography and 91% of patients underwent primary PCI. Using a threshold of AHI ≥ 5 events/hour, SA was present in 65.7% of patients after acute MI. Mild SA was present in 32.6%, moderate in 20.4% and severe in 12.7%. The day-night variation in the onset of MI in all groups of SA patients was similar to that observed in non-SA patients. From 6AM–12PM, the frequency of MI was higher in both SA and non-SA patients, as compared to the interval from 12AM–6AM (all p<0.05). Conclusion There is a high prevalence of SA in patients presenting with acute MI. Peak time of MI onset in SA patients was between 6AM–noon, similar to that in the general population. Whether diagnosis and treatment of SA after MI will significantly improve outcomes in these patients remains to be determined. PMID:25064202

  3. Spatial selectivity in the temporoparietal junction, inferior frontal sulcus, and inferior parietal lobule

    PubMed Central

    Hansen, Kathleen A.; Chu, Carlton; Dickinson, Annelise; Pye, Brandon; Weller, J. Patrick; Ungerleider, Leslie G.

    2015-01-01

    Spatial selectivity, as measured by functional magnetic resonance imaging (fMRI) activity patterns that vary consistently with the location of visual stimuli, has been documented in many human brain regions, notably the occipital visual cortex and the frontal and parietal regions that are active during endogenous, goal-directed attention. We hypothesized that spatial selectivity also exists in regions that are active during exogenous, stimulus-driven attention. To test this hypothesis, we acquired fMRI data while subjects maintained passive fixation. At jittered time intervals, a briefly presented wedge-shaped array of rapidly expanding circles appeared at one of three contralateral or one of three ipsilateral locations. Positive fMRI activations were identified in multiple brain regions commonly associated with exogenous attention, including the temporoparietal junction, the inferior parietal lobule, and the inferior frontal sulcus. These activations were not organized as a map across the cortical surface. However, multivoxel pattern analysis of the fMRI activity correctly classified every pair of stimulus locations, demonstrating that patterns of fMRI activity were correlated with spatial location. These observations held for both contralateral and ipsilateral stimulus pairs as well as for stimuli of different textures (radial checkerboard) and shapes (squares and rings). Permutation testing verified that the obtained accuracies were not due to systematic biases and demonstrated that the findings were statistically significant. PMID:26382006

  4. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    SciTech Connect

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  5. HIF-1α downregulates miR-17/20a directly targeting p21 and STAT3: a role in myeloid leukemic cell differentiation.

    PubMed

    He, M; Wang, Q-Y; Yin, Q-Q; Tang, J; Lu, Y; Zhou, C-X; Duan, C-W; Hong, D-L; Tanaka, T; Chen, G-Q; Zhao, Q

    2013-03-01

    Hypoxia-inducible factor 1 (HIF-1) is a crucial transcription factor for the cellular adaptive response to hypoxia, which contributes to multiple events in cancer biology. MicroRNAs (miRNAs) are involved in almost all cellular activities such as differentiation, proliferation, and apoptosis. In this work, we use miRNA microarrays to profile miRNA expression in acute myeloid leukemia (AML) cells with inducible HIF-1α expression, and identify 19 differentially expressed miRNAs. Our study shows that HIF-1α represses the expression of miR-17 and miR-20a by downregulating c-Myc expression. These two miRNAs alleviate hypoxia and HIF-1α-induced differentiation of AML cells. More intriguingly, miR-17 and miR-20a directly inhibit the p21 and STAT3 (signal transducer and activator of transcription 3) expression, both of which can reverse miR-17/miR-20a-mediated abrogation of HIF-1α-induced differentiation. Moreover, we show in vivo that miR-20a contributes to HIF-1α-induced differentiation of leukemic cells. Taken together, our results suggest that HIF-1α regulates the miRNA network to interfere with AML cell differentiation, representing a novel molecular mechanism for HIF-1-mediated anti-leukemic action. PMID:23059786

  6. Inferior vena cava stenosis: Echocardiographic diagnosis in Marfan syndrome

    PubMed Central

    Ghazal, Sami Nimer; Ouf, Shady G

    2015-01-01

    Marfan syndrome is a genetic disease with variable clinical presentation. This case describes a 36-year-old lady who was diagnosed with Marfan syndrome based on revised Ghent criteria. She was found to have bicuspid aortic valve and sensorineural hearing loss. Inferior vena cava stenosis was suspected on echocardiography due to high velocity flow and visualization of a focal narrowing in the inferior vena cava proximal to hepatic vein entry. Inferior vena cava stenosis was confirmed by computed tomography. Echocardiographic features suggestive of inferior vena cava stenosis include detection of a focal narrowing and high turbulent flow, peak velocity > 1.5 m/s and S/D wave fusion on spectral Doppler. PMID:26925409

  7. Anatomical variation of the inferior mesenteric vein's drainage pattern

    NASA Astrophysics Data System (ADS)

    Zilaie, Mina

    The purpose of this project is to report the variable drainage pattern of the inferior mesenteric vein (IMV) as reported by medical students' observations recorded on anatomical variation data sheets (n = 192). A meta-analysis on the drainage pattern of the inferior mesenteric vein as described in various anatomy resources was conducted (n = 40). The inferior mesenteric vein was observed to drain into the splenic vein, the superior mesenteric vein, and the junction between the superior mesenteric vein and the splenic vein. Anatomy resources do not commonly report all three drainage sites. It is imperative that all these common drainage sites of the inferior mesenteric vein are stated in anatomy resources, so that students are taught realistic human anatomy including its common variations.

  8. Troubleshooting OptEase inferior vena cava filter retrieval.

    PubMed

    Nakashima, Masaya; Kobayashi, Hideaki; Kobayashi, Masayoshi

    2016-01-01

    For treatment of deep vein thrombosis and prevention of pulmonary thromboembolism, a retrievable inferior vena cava filter is commonly utilized as an effective bridge to anticoagulation. However, we have experienced difficulties in retrieving inferior vena cava filters. Endovascular retrieval assisted by disposable biopsy forceps is an appropriate approach because it provides a less-invasive low-cost way to remove a migrated filter. We suggest this troubleshooting technique to deal with filter hook migration into the caval wall. PMID:24828829

  9. Patellar Shape-Memory Fixator for the Treatment of Comminuted Fractures of the Inferior Pole of the Patella

    NASA Astrophysics Data System (ADS)

    Liu, Xin-Wei; Shang, Hui-Juan; Xu, Shuo-Gui; Wang, Zhi-Wei; Zhang, Chun-Cai; Fu, Qing-Ge

    2011-07-01

    Comminuted and displaced fractures of the inferior pole of the patella are not easy to reduce and it is difficult to fix the fragments soundly enough to allow early movement of the knee. The purpose of this study is to evaluate the clinical effectiveness of the internal fixation technique with Patellar Shape-Memory Fixator (PSMF) in acute comminuted fractures of the inferior pole of the patella. We retrospectively studied 25 patients with comminuted fractures of the inferior pole of the patella who were treated with PSMF and followed up for a mean period of 26 months (14 to 60). All the fractures healed at a mean of 6 weeks (5 to 7). The mean grading at the final follow-up was 29.5 points (27 to 30) using the Bostman score, with no observable restriction of movement. No breakage of the PSMF or infection occurred. No delayed union, nonunion, and infection were seen. This technique preserved the length of the patella, reduced the comminuted fragments of the inferior pole and avoided long-term immobilization of the knee.

  10. Prospective clinical, scintigraphic, angiographic and functional evaluation of patients after inferior myocardial infarction with and without right ventricular dysfunction

    SciTech Connect

    Haines, D.E.; Beller, G.A.; Watson, D.D.; Nygaard, T.W.; Craddock, G.B.; Cooper, A.A.; Gibson, R.S.

    1985-11-01

    To elucidate the functional and prognostic significance of right ventricular dysfunction after acute inferior wall myocardial infarction, 74 consecutive patients with inferior infarction were prospectively evaluated with gated equilibrium blood pool imaging at rest, submaximal exercise thallium-201 scintigraphy and coronary angiography before hospital discharge. In addition, symptom-limited stress thallium-201 scintigraphy was performed in 61 patients at 3 months, and all patients were followed up clinically for 23 +/- 15 months. Utilizing predetermined radionuclide angiographic criteria, 47 patients (Group I) had normal right ventricular function, 12 patients (Group II) had mild to moderate dysfunction and 15 patients (Group III) had severe right ventricular dysfunction. Exercise tolerance as assessed by treadmill time, blood pressure-heart rate product and peak work load in METS was comparable among the three groups, both before hospital discharge and at 3 month follow-up. No differences in indicators of exercise-induced ischemia were noted among the groups, including the prevalence of redistribution thallium-201 defects, ST segment depression or symptoms of chest pain. Finally, cardiac mortality, reinfarction rate and the incidence of medically refractory angina pectoris were similar in the three groups. Thus, right ventricular dysfunction after acute inferior wall myocardial infarction does not appear to limit exercise tolerance or identify a subgroup of patients at higher risk for recurrent cardiac events.

  11. miRNAs Related to Skeletal Diseases.

    PubMed

    Seeliger, Claudine; Balmayor, Elizabeth R; van Griensven, Martijn

    2016-09-01

    miRNAs as non-coding, short, double-stranded RNA segments are important for cellular biological functions, such as proliferation, differentiation, and apoptosis. miRNAs mainly contribute to the inhibition of important protein translations through their cleavage or direct repression of target messenger RNAs expressions. In the last decade, miRNAs got in the focus of interest with new publications on miRNAs in the context of different diseases. For many types of cancer or myocardial damage, typical signatures of local or systemically circulating miRNAs have already been described. However, little is known about miRNA expressions and their molecular effect in skeletal diseases. An overview of published studies reporting miRNAs detection linked with skeletal diseases was conducted. All regulated miRNAs were summarized and their molecular interactions were illustrated. This review summarizes the involvement and interaction of miRNAs in different skeletal diseases. Thereby, 59 miRNAs were described to be deregulated in tissue, cells, or in the circulation of osteoarthritis (OA), 23 miRNAs deregulated in osteoporosis, and 107 miRNAs deregulated in osteosarcoma (OS). The molecular influences of miRNAs regarding OA, osteoporosis, and OS were illustrated. Specific miRNA signatures for skeletal diseases are described in the literature. Some overlapped, but also unique ones for each disease exist. These miRNAs may present useful targets for the development of new therapeutic approaches and are candidates for diagnostic evaluations. PMID:27418331

  12. The spectrum of right ventricular involvement in inferior wall myocardial infarction: a clinical, hemodynamic and noninvasive study

    SciTech Connect

    Baigrie, R.S.; Haq, A.; Morgan, C.D.; Rakowski, H.; Drobac, M.; McLaughlin, P.

    1983-06-01

    The clinical experience with 37 patients with acute transmural inferior wall myocardial infarction who were assessed for evidence of right ventricular involvement is reported. On the basis of currently accepted hemodynamic criteria, 29 patients (78%) had evidence suggestive of right ventricular infarction. However, only 5 (20%) of 25 patients demonstrated right ventricular uptake of technetium pyrophosphate on scintigraphy. Two-dimensional echocardiography or isotope nuclear angiography, or both, were performed in 32 patients; 20 studies (62%) showed evidence of right ventricular wall motion disturbance or dilation, or both. Twenty-one patients demonstrated a late inspiratory increase in the jugular venous pressure (Kussmaul's sign). The presence of this sign in the clinical setting of inferior wall myocardial infarction was predictive for right ventricular involvement in 81% of the patients in this study. It is suggested that right ventricular involvement in this clinical setting is common and includes not only infarction but also dysfunction without detectable infarction, which is likely on an ischemic basis.

  13. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia.

    PubMed

    Garzon, R; Pichiorri, F; Palumbo, T; Visentini, M; Aqeilan, R; Cimmino, A; Wang, H; Sun, H; Volinia, S; Alder, H; Calin, G A; Liu, C-G; Andreeff, M; Croce, C M

    2007-06-14

    MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-kappaB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-kappaB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/miR-16-1, respectively. PMID:17260024

  14. Expression of miRNA-122 Induced by Liver Toxicants in Zebrafish

    PubMed Central

    Jeong, Yun-Mi; Ryu, Jeong-Im; Choi, Tae-Young; Bae, Myung-Ae; Son, Woo-Chan

    2016-01-01

    MicroRNA-122 (miRNA-122), also known as liver-specific miRNA, has recently been shown to be a potent biomarker in response to liver injury in mammals. The objective of this study was to examine its expression in response to toxicant treatment and acute liver damage, using the zebrafish system as an alternative model organism. For the hepatotoxicity assay, larval zebrafish were arrayed in 24-well plates. Adult zebrafish were also tested and arrayed in 200 mL cages. Animals were exposed to liver toxicants (tamoxifen or acetaminophen) at various doses, and miRNA-122 expression levels were analyzed using qRT-PCR in dissected liver, brain, heart, and intestine, separately. Our results showed no significant changes in miRNA-122 expression level in tamoxifen-treated larvae; however, miRNA-122 expression was highly induced in tamoxifen-treated adults in a tissue-specific manner. In addition, we observed a histological change in adult liver (0.5 μM) and cell death in larval liver (5 μM) at different doses of tamoxifen. These results indicated that miRNA-122 may be utilized as a liver-specific biomarker for acute liver toxicity in zebrafish. PMID:27563662

  15. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC

    PubMed Central

    Fornari, Francesca; Ferracin, Manuela; Trerè, Davide; Milazzo, Maddalena; Marinelli, Sara; Galassi, Marzia; Venerandi, Laura; Pollutri, Daniela; Patrizi, Clarissa; Borghi, Alberto; Foschi, Francesco G.; Stefanini, Giuseppe F.; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura

    2015-01-01

    The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment. PMID:26509672

  16. The effects of inferior olive lesion on strychnine seizure

    SciTech Connect

    Anderson, M.C.; Chung, E.Y.; Van Woert, M.H. )

    1990-10-01

    Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable ({sup 3}H)AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding in cerebella from inferior olive-lesioned rats was observed, but no difference in ({sup 3}H)AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10 imine) were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the ({sup 3}H)AMPA binding data.

  17. Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion–induced injury

    PubMed Central

    Chen, Hsi-Hsien; Lan, Yi-Fan; Li, Hsiao-Fen; Cheng, Ching-Feng; Lai, Pei-Fang; Li, Wei-Hua; Lin, Heng

    2016-01-01

    Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3′UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells. The CCAAT enhancer binding protein beta (C/EBP-β) increased the expression of miR-16 after I/R injury. The ChIP and luciferase promoter assay indicated that about −1.0 kb to −0.5 kb upstream of miR-16 genome promoter region containing C/EBP-β binding motif transcriptionally regulated miR-16 expression. Meanwhile, the level of pri-miR-16 was higher in mice infected with lentivirus containing C/EBP-β compared with wild-type (WT) mice and overexpression of C/EBP-β in the kidney of WT mice reduced kidney function, increased kidney apoptosis, and elevated urinary miR-16 level. Our results indicated that miR-16 was transactivated by C/EBP-β resulting in aggravated I/R induced AKI and that urinary miR-16 may serve as a potential biomarker for AKI. PMID:27297958

  18. Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion-induced injury.

    PubMed

    Chen, Hsi-Hsien; Lan, Yi-Fan; Li, Hsiao-Fen; Cheng, Ching-Feng; Lai, Pei-Fang; Li, Wei-Hua; Lin, Heng

    2016-01-01

    Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3'UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells. The CCAAT enhancer binding protein beta (C/EBP-β) increased the expression of miR-16 after I/R injury. The ChIP and luciferase promoter assay indicated that about -1.0 kb to -0.5 kb upstream of miR-16 genome promoter region containing C/EBP-β binding motif transcriptionally regulated miR-16 expression. Meanwhile, the level of pri-miR-16 was higher in mice infected with lentivirus containing C/EBP-β compared with wild-type (WT) mice and overexpression of C/EBP-β in the kidney of WT mice reduced kidney function, increased kidney apoptosis, and elevated urinary miR-16 level. Our results indicated that miR-16 was transactivated by C/EBP-β resulting in aggravated I/R induced AKI and that urinary miR-16 may serve as a potential biomarker for AKI. PMID:27297958

  19. Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis.

    PubMed

    Roca-Alonso, L; Castellano, L; Mills, A; Dabrowska, A F; Sikkel, M B; Pellegrino, L; Jacob, J; Frampton, A E; Krell, J; Coombes, R C; Harding, S E; Lyon, A R; Stebbing, J

    2015-01-01

    The use of anthracyclines such as doxorubicin (DOX) has improved outcome in cancer patients, yet associated risks of cardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity is frequently irreversible and typically progresses to heart failure (HF) but our understanding of molecular mechanisms underlying this and essential for development of cardioprotective strategies remains largely obscure. As microRNAs (miRNAs) have been shown to play potent regulatory roles in both cardiovascular disease and cancer, we investigated miRNA changes in DOX-induced HF and the alteration of cellular processes downstream. Myocardial miRNA profiling was performed after DOX-induced injury, either via acute application to isolated cardiomyocytes or via chronic exposure in vivo, and compared with miRNA profiles from remodeled hearts following myocardial infarction. The miR-30 family was downregulated in all three models. We describe here that miR-30 act regulating the β-adrenergic pathway, where preferential β1- and β2-adrenoceptor (β1AR and β2AR) direct inhibition is combined with Giα-2 targeting for fine-tuning. Importantly, we show that miR-30 also target the pro-apoptotic gene BNIP3L/NIX. In aggregate, we demonstrate that high miR-30 levels are protective against DOX toxicity and correlate this in turn with lower reactive oxygen species generation. In addition, we identify GATA-6 as a mediator of DOX-associated reductions in miR-30 expression. In conclusion, we describe that DOX causes acute and sustained miR-30 downregulation in cardiomyocytes via GATA-6. miR-30 overexpression protects cardiac cells from DOX-induced apoptosis, and its maintenance represents a potential cardioprotective and anti-tumorigenic strategy for anthracyclines. PMID:25950484

  20. Acute coronary syndrome in pregnant women.

    PubMed

    El-Deeb, Mohammed; El-Menyar, Ayman; Gehani, Abdulrazzak; Sulaiman, Kadhim

    2011-04-01

    The purpose of this article is to review the available information on the pathophysiology, diagnosis, treatment and prognosis of acute coronary syndromes (ST-elevation myocardial infarction [STEMI] and non-ST-elevation myocardial infarction [NSTEMI]) during all stages of pregnancy. We searched the English-language literature indexed in MEDLINE, Scopus and EBSCO host research databases from 1980 through to August 2010 using the indexing terms 'pregnancy', 'ante-,peri-, and postpartum', 'acute coronary syndrome', 'myocardial infarction', 'STEMI' and 'NSTEMI'. Symptomatic coronary artery disease is still infrequent in women of childbearing age, but the recent increase in its prevalence in pregnancy has been attributed to the modern trend of childbearing in older years because many young working women are postponing having children. Although rare, acute pregnancy-related MI is a devastating event that may claim the life of a mother and her fetus. The incidence of MI is estimated at 0.6-1 per 10,000 pregnancies. The case fatality rate has been reported to be 5-37%. Owing to the rarity of the event, information related to MI in pregnancy is derived from case reports and, therefore, is subject to considerable reporting bias. Treatment needs to be prompt and urgent because of the very high mortality rate. Current guidelines for the diagnosis and treatment of MI should be expanded to include pregnancy-related MI. Screening and management of cardiovascular risk factors should be achieved before pregnancy. PMID:21517733

  1. Adaptive coupling of inferior olive neurons in cerebellar learning.

    PubMed

    Tokuda, Isao T; Hoang, Huu; Schweighofer, Nicolas; Kawato, Mitsuo

    2013-11-01

    In the cerebellar learning hypothesis, inferior olive neurons are presumed to transmit high fidelity error signals, despite their low firing rates. The idea of chaotic resonance has been proposed to realize efficient error transmission by desynchronized spiking activities induced by moderate electrical coupling between inferior olive neurons. A recent study suggests that the coupling strength between inferior olive neurons can be adaptive and may decrease during the learning process. We show that such a decrease in coupling strength can be beneficial for motor learning, since efficient coupling strength depends upon the magnitude of the error signals. We introduce a scheme of adaptive coupling that enhances the learning of a neural controller for fast arm movements. Our numerical study supports the view that the controlling strategy of the coupling strength provides an additional degree of freedom to optimize the actual learning in the cerebellum. PMID:23337637

  2. Traumatic neuroma of the inferior alveolar nerve: a case report.

    PubMed

    Arribas-García, Ignacio; Alcalá-Galiano, Andrea; Gutiérrez, Ramón; Montalvo-Moreno, Juan José

    2008-03-01

    Traumatic neuromas are rare entities which characteristically arise subsequently to surgery and are usually accompanied by pain, typically neuralgic. We present an unusual case of an intraosseous traumatic neuroma of the inferior alveolar nerve following tooth extraction. A 56-year-old man consulted for paresthesias and hyperesthesia in the left mandibular region following extraction of the left mandibular third molar (#38). The panoramic radiograph revealed a radiolucent lesion in the inferior alveolar nerve canal, and CT demonstrated the existence of a mass within the canal, producing widening of the same. Nerve-sparing excisional biopsy was performed. Histopathology and immunohistochemistry were consistent with traumatic neuroma of the left inferior alveolar nerve. After 3 years of follow-up, the patient is asymptomatic and there are no signs of recurrence. PMID:18305440

  3. Inferior oblique recession in thyroid-related orbitopathy.

    PubMed

    Salchow, Daniel J

    2015-06-01

    Thyroid-related orbitopathy is a form of orbital inflammation associated with thyroid dysfunction, developing in many patients with Graves disease. Fibrosis of the inferior rectus muscle can lead to restricted elevation and vertical ocular misalignment, which may be improved by recessing this muscle. In some patients, vertical misalignment persists after surgical weakening of one or more vertical rectus muscles. In this case series, unilateral inferior oblique recession as a secondary procedure after inferior rectus recession reduced hypertropia in primary gaze from 9(Δ) ± 3(Δ) to 1.3(Δ) ± 1.5(Δ) (mean ± standard deviation) and largest hypertropia in side gaze from 18.3 ± 2.1(Δ) to 3.3(Δ) ± 1.5(Δ). Postoperatively, all 3 patients were diplopia free in primary and downgaze. PMID:26059675

  4. Variant Inferior Alveolar Nerves and Implications for Local Anesthesia.

    PubMed

    Wolf, Kevin T; Brokaw, Everett J; Bell, Andrea; Joy, Anita

    2016-01-01

    A sound knowledge of anatomical variations that could be encountered during surgical procedures is helpful in avoiding surgical complications. The current article details anomalous morphology of inferior alveolar nerves encountered during routine dissection of the craniofacial region in the Gross Anatomy laboratory. We also report variations of the lingual nerves, associated with the inferior alveolar nerves. The variations were documented and a thorough review of literature was carried out. We focus on the variations themselves, and the clinical implications that these variations present. Thorough understanding of variant anatomy of the lingual and inferior alveolar nerves may determine the success of procedural anesthesia, the etiology of pathologic processes, and the avoidance of surgical misadventure. PMID:27269666

  5. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

    PubMed

    Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

    2016-01-01

    Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions. PMID:27137489

  6. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  7. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  8. MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2

    PubMed Central

    Tong, Zhongyi; Jiang, Bimei; Wu, Yanyang; Liu, Yanjuan; Li, Yuanbin; Gao, Min; Jiang, Yu; Lv, Qinglan; Xiao, Xianzhong

    2015-01-01

    Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2. PMID:26132560

  9. A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA.

    PubMed

    Suryawanshi, Hemant; Sarangdhar, Mayuresh Anant; Vij, Manika; Roshan, Reema; Singh, Vijay Pal; Ganguli, Munia; Pillai, Beena

    2015-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression. In the brain, vital processes like neurodevelopment and neuronal functions depend on the correct expression of microRNAs. Perturbation of microRNAs in the brain can be used to model neurodegenerative diseases by modulating neuronal cell death. Currently, stereotactic injection is used to deliver miRNA knockdown agents to specific location in the brain. Here, we discuss strategies to design antagomirs against miRNA with locked nucleotide modifications (LNA). Subsequently describe a method for brain specific delivery of antagomirs, uniformly across different regions of the brain. This method is simple and widely applicable since it overcomes the surgery, associated injury and limitation of local delivery in stereotactic injections. We prepared a complex of neurotropic, cell-penetrating peptide Rabies Virus Glycoprotein (RVG) with antagomir against miRNA-29 and injected through tail vein, to specifically deliver in the brain. The antagomir design incorporated features that allow specific targeting of the miRNA and formation of non-covalent complexes with the peptide. The knock-down of the miRNA in neuronal cells, resulted in apoptotic cell death and associated behavioural defects. Thus, the method can be used for acute models of neuro-degeneration through the perturbation of miRNAs. PMID:26779762

  10. An emerging role for the miR-26 family in cardiovascular disease

    PubMed Central

    Icli, Basak; Dorbala, Pranav; Feinberg, Mark W.

    2014-01-01

    In response to acute myocardial infarction (MI), a complex series of cellular and molecular signaling events orchestrate the myocardial remodeling that ensues weeks to months after injury. Clinical, epidemiological, and pathological studies demonstrate that inadequate or impaired angiogenesis after myocardial injury is often associated with decreased left ventricular (LV) function and clinical outcomes. The microRNA family, miR-26, plays diverse roles in regulating key aspects of cellular growth, development, and activation. Recent evidence supports a central role for the miR-26 family in cardiovascular disease by controlling critical signaling pathways, such as BMP/SMAD1 signaling, and targets relevant to endothelial cell growth, angiogenesis, and LV function post-MI. Emerging studies of the miR-26 family in other cell types including vascular smooth muscle cells, cardiac fibroblasts, and cardiomyocytes suggest that miR-26 may bear important implications for a range of cardiovascular repair mechanisms. This review examines the current knowledge of the miR-26 family’s role in key cell types that critically control cardiovascular disease under pathological and physiological stimuli PMID:25066487

  11. microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia.

    PubMed

    Correia, Nádia C; Melão, Alice; Póvoa, Vanda; Sarmento, Leonor; Gómez de Cedrón, Marta; Malumbres, Marcos; Enguita, Francisco J; Barata, João T

    2016-02-16

    The transcription factor TAL1 is a proto-oncogene whose aberrant expression in committed T-cell precursors is associated with the development of T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms leading to aberrant activation of TAL1 in T-ALL patients who lack chromosomal rearrangements involving the TAL1 locus remain largely unknown. We hypothesized that TAL1 levels decrease during normal T-cell development at least in part due to miRNA-dependent silencing, in which case TAL1 over-expression in some T-ALL cases could be the consequence of deregulated miRNA expression. By performing computational prediction of miRNAs that bind to the human TAL1 mRNA we compiled a list of miRNAs that are candidates to regulate TAL1. Using a luciferase reporter system and mutagenesis assays we confirmed the miRNA-TAL1 mRNA interactions and selected candidate miRNAs: miR-101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p. Over-expression of these microRNAs in different T-ALL cell lines consistently resulted in the down-regulation of TAL1 protein. In accordance, inhibition of miR-101 and miR-520d-5p promoted TAL1 protein expression. Importantly, we found that miR-101, miR-140-5p, miR-448 and miR-485-5p were down-regulated in T-ALL patient specimens and T-ALL cell lines. Our results show for the first time the existence of epigenetic regulation of TAL1 by specific miRNAs which may contribute, at least in part, to the ectopic expression of TAL1 in some T-ALL cases. PMID:26882564

  12. microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia

    PubMed Central

    Correia, Nádia C.; Melão, Alice; Póvoa, Vanda; Sarmento, Leonor; de Cedrón, Marta Gómez; Malumbres, Marcos; Enguita, Francisco J.; Barata, João T.

    2016-01-01

    The transcription factor TAL1 is a proto-oncogene whose aberrant expression in committed T-cell precursors is associated with the development of T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms leading to aberrant activation of TAL1 in T-ALL patients who lack chromosomal rearrangements involving the TAL1 locus remain largely unknown. We hypothesized that TAL1 levels decrease during normal T-cell development at least in part due to miRNA-dependent silencing, in which case TAL1 over-expression in some T-ALL cases could be the consequence of deregulated miRNA expression. By performing computational prediction of miRNAs that bind to the human TAL1 mRNA we compiled a list of miRNAs that are candidates to regulate TAL1. Using a luciferase reporter system and mutagenesis assays we confirmed the miRNA-TAL1 mRNA interactions and selected candidate miRNAs: miR-101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p. Over-expression of these microRNAs in different T-ALL cell lines consistently resulted in the down-regulation of TAL1 protein. In accordance, inhibition of miR-101 and miR-520d-5p promoted TAL1 protein expression. Importantly, we found that miR-101, miR-140-5p, miR-448 and miR-485-5p were down-regulated in T-ALL patient specimens and T-ALL cell lines. Our results show for the first time the existence of epigenetic regulation of TAL1 by specific miRNAs which may contribute, at least in part, to the ectopic expression of TAL1 in some T-ALL cases. PMID:26882564

  13. Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation

    PubMed Central

    Tam, Yuk Him; Ma, Terence Ping Yuen; Lam, Hugh Simon; Cheung, Hon Ming; Lee, Kim Hung; To, Ka Fai; Li, Karen

    2015-01-01

    Background Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology. Methods We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples. Results We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction. Conclusions The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology. PMID:26274503

  14. miRiadne: a web tool for consistent integration of miRNA nomenclature.

    PubMed

    Bonnal, Raoul J P; Rossi, Riccardo L; Carpi, Donatella; Ranzani, Valeria; Abrignani, Sergio; Pagani, Massimiliano

    2015-07-01

    The miRBase is the official miRNA repository which keeps the annotation updated on newly discovered miRNAs: it is also used as a reference for the design of miRNA profiling platforms. Nomenclature ambiguities generated by loosely updated platforms and design errors lead to incompatibilities among platforms, even from the same vendor. Published miRNA lists are thus generated with different profiling platforms that refer to diverse and not updated annotations. This greatly compromises searches, comparisons and analyses that rely on miRNA names only without taking into account the mature sequences, which is particularly critic when such analyses are carried over automatically. In this paper we introduce miRiadne, a web tool to harmonize miRNA nomenclature, which takes into account the original miRBase versions from 10 up to 21, and annotations of 40 common profiling platforms from nine brands that we manually curated. miRiadne uses the miRNA mature sequence to link miRBase versions and/or platforms to prevent nomenclature ambiguities. miRiadne was designed to simplify and support biologists and bioinformaticians in re-annotating their own miRNA lists and/or data sets. As Ariadne helped Theseus in escaping the mythological maze, miRiadne will help the miRNA researcher in escaping the nomenclature maze. miRiadne is freely accessible from the URL http://www.miriadne.org. PMID:25897123

  15. miRiadne: a web tool for consistent integration of miRNA nomenclature

    PubMed Central

    Bonnal, Raoul J. P.; Rossi, Riccardo L.; Carpi, Donatella; Ranzani, Valeria; Abrignani, Sergio; Pagani, Massimiliano

    2015-01-01

    The miRBase is the official miRNA repository which keeps the annotation updated on newly discovered miRNAs: it is also used as a reference for the design of miRNA profiling platforms. Nomenclature ambiguities generated by loosely updated platforms and design errors lead to incompatibilities among platforms, even from the same vendor. Published miRNA lists are thus generated with different profiling platforms that refer to diverse and not updated annotations. This greatly compromises searches, comparisons and analyses that rely on miRNA names only without taking into account the mature sequences, which is particularly critic when such analyses are carried over automatically. In this paper we introduce miRiadne, a web tool to harmonize miRNA nomenclature, which takes into account the original miRBase versions from 10 up to 21, and annotations of 40 common profiling platforms from nine brands that we manually curated. miRiadne uses the miRNA mature sequence to link miRBase versions and/or platforms to prevent nomenclature ambiguities. miRiadne was designed to simplify and support biologists and bioinformaticians in re-annotating their own miRNA lists and/or data sets. As Ariadne helped Theseus in escaping the mythological maze, miRiadne will help the miRNA researcher in escaping the nomenclature maze. miRiadne is freely accessible from the URL http://www.miriadne.org. PMID:25897123

  16. Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis

    PubMed Central

    Rothnie, Kieran J; Yan, Ruoling; Smeeth, Liam; Quint, Jennifer K

    2015-01-01

    Objectives Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. Design Systematic review and meta-analysis. Methods MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. Results Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). Conclusions There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. PMID:26362660

  17. Serum miRNAs panel (miR-16-2*, miR-195, miR-2861, miR-497) as novel non-invasive biomarkers for detection of cervical cancer

    PubMed Central

    Zhang, Yujuan; Zhang, Donghong; Wang, Fei; Xu, Danfei; Guo, Ye; Cui, Wei

    2015-01-01

    miRNAs have been established as critical layer of regulation during tumorigenesis; extracellular miRNAs are extraordinarily stable; and, quantitative reverse transcript polymerase chain reaction (qRT-PCR) provides a sensitive platform for quantifying miRNAs with a broad dynamic range. Herein, we aimed to establish a serum miRNA signature for diagnosing cervical cancer (CC). In this study, we recruited a cohort of 184 CC, 186 cervical intraepithelial neoplasia (CIN) patients and 193 healthy control subjects. qRT-PCR was performed with serum samples to screen a pool of 444 miRNAs at the initial phase, 66 miRNAs at the training phase, and 7 miRNAs at the validation phase. The profile of 4 circulating miRNAs (miR-16-2*, miR-195, miR-2861, miR-497) was established for CC diagnosis. By Receiver Operating Characteristic (ROC) curve analysis, this 4-miRNA signature showed high accuracy in discriminating CC (AUC = 0.849), and CIN individuals (AUC = 0.734) from healthy controls. Among these 4 miRNAs, only miR-16-2*, but not miR-195, miR-2861 or miR497, shared a similar pattern in sera of breast cancer and ovarian cancer patients. Overall, our studies have identified a novel noninvasive biomarker constituted with a panel of four miRNAs (miR-16-2*, miR-195, miR-2861, miR-497). PMID:26656154

  18. Research on MI in Equipoise

    PubMed Central

    Zuckoff, Allan; Dew, Mary Amanda

    2012-01-01

    Residual ambivalence prior to live organ donation has been shown to predict worse physical and psychological outcomes for the donor following surgery. We are studying whether MI can help individuals who have agreed to become living organ donors to resolve residual ambivalence about their decision. In this situation, ethical practice demands that the counselor take up a stance of equipoise, equally welcoming of strengthened resolve to donate or a decision not to do so. This paper describes our adaptations of MI for this unique application. PMID:23106035

  19. Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP

    PubMed Central

    Hatzl, Stefan; Geiger, Olivia; Kuepper, Maja Kim; Caraffini, Veronica; Seime, Till; Furlan, Tobias; Nussbaumer, Erika; Wieser, Rotraud; Pichler, Martin; Scheideler, Marcel; Nowek, Katarzyna; Jongen-Lavrencic, Mojca; Quehenberger, Franz; Wölfler, Albert; Troppmair, Jakob; Sill, Heinz; Zebisch, Armin

    2016-01-01

    RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3′-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a–binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a–binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. PMID:27197200

  20. Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP.

    PubMed

    Hatzl, Stefan; Geiger, Olivia; Kuepper, Maja Kim; Caraffini, Veronica; Seime, Till; Furlan, Tobias; Nussbaumer, Erika; Wieser, Rotraud; Pichler, Martin; Scheideler, Marcel; Nowek, Katarzyna; Jongen-Lavrencic, Mojca; Quehenberger, Franz; Wölfler, Albert; Troppmair, Jakob; Sill, Heinz; Zebisch, Armin

    2016-06-15

    RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3'-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a-binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a-binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. Cancer Res; 76(12); 3644-54. ©2016 AACR. PMID:27197200

  1. Epigenetic Regulation of miRNA-211 by MMP-9 Governs Glioma Cell Apoptosis, Chemosensitivity and Radiosensitivity

    PubMed Central

    Asuthkar, Swapna; Velpula, Kiran Kumar; Chetty, Chandramu; Gorantla, Bharathi; Rao, Jasti S.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most aggressive brain cancer, and to date, no curative treatment has been developed. In this study, we report that miR-211, a microRNA predicted to target MMP-9, is suppressed in grade IV GBM specimens. Furthermore, we found that miR-211 suppression in GBM involves aberrant methylation-mediated epigenetic silencing of the miR-211 promoter. Indeed, we observed a highly significant inverse correlation between miR-211 expression and MMP-9 protein levels, which is indicative of post-transcriptional control of gene expression. Additionally, shRNA specific for MMP-9 (pM) promoted miR-211 expression via demethylation of miR-211 promoter-associated CpG islands (-140 to +56). In independent experiments, we confirmed that miR-211 overexpression and pM treatments led to the activation of the intrinsic mitochondrial/Caspase-9/3-mediated apoptotic pathway in both glioma cells and cancer stem cells (CSC). We also investigated whether miR-211 is involved in the regulation of MMP-9 and thus plays a functional role in GBM. We found an acute inhibitory effect of miR-211 on glioma cell invasion and migration via suppression of MMP-9. Given the insensitivity of some GBMs to radiation and chemotherapy (temozolomide) along with the hypothesis that glioma CSC cause resistance to therapy, our study indicates that miR-211 or pM in combination with ionizing radiation (IR) and temozolomide significantly induces apoptosis and DNA fragmentation. Of note, miR-211- and pM-treated CSC demonstrated increased drug retention capacity, as observed by MDR1/P-gp mediated-Rhodamine 123 drug efflux activity assay. These results suggest that either rescuing miR-211 expression or downregulation of MMP-9 may have a new therapeutic application for GBM patients in the future. PMID:23183822

  2. Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis, chemosensitivity and radiosensitivity.

    PubMed

    Asuthkar, Swapna; Velpula, Kiran Kumar; Chetty, Chandramu; Gorantla, Bharathi; Rao, Jasti S

    2012-11-01

    Glioblastoma multiforme (GBM) is the most aggressive brain cancer, and to date, no curative treatment has been developed. In this study, we report that miR-211, a microRNA predicted to target MMP-9, is suppressed in grade IV GBM specimens. Furthermore, we found that miR-211 suppression in GBM involves aberrant methylation-mediated epigenetic silencing of the miR-211 promoter. Indeed, we observed a highly significant inverse correlation between miR-211 expression and MMP-9 protein levels, which is indicative of post-transcriptional control of gene expression. Additionally, shRNA specific for MMP-9 (pM) promoted miR-211 expression via demethylation of miR-211 promoter-associated CpG islands (-140 to +56). In independent experiments, we confirmed that miR-211 overexpression and pM treatments led to the activation of the intrinsic mitochondrial/Caspase-9/3-mediated apoptotic pathway in both glioma cells and cancer stem cells (CSC). We also investigated whether miR-211 is involved in the regulation of MMP-9 and thus plays a functional role in GBM. We found an acute inhibitory effect of miR-211 on glioma cell invasion and migration via suppression of MMP-9. Given the insensitivity of some GBMs to radiation and chemotherapy (temozolomide) along with the hypothesis that glioma CSC cause resistance to therapy, our study indicates that miR-211 or pM in combination with ionizing radiation (IR) and temozolomide significantly induces apoptosis and DNA fragmentation. Of note, miR-211- and pM-treated CSC demonstrated increased drug retention capacity, as observed by MDR1/P-gp mediated-Rhodamine 123 drug efflux activity assay. These results suggest that either rescuing miR-211 expression or downregulation of MMP-9 may have a new therapeutic application for GBM patients in the future. PMID:23183822

  3. Asymptomatic Lumbar Vertebral Erosion from Inferior Vena Cava Filter Perforation

    SciTech Connect

    Fang, Wayne Hieb, Robert A.; Olson, Eric; Carrera, Guillermo F.

    2007-06-15

    In 2002, a 24-year-old female trauma patient underwent prophylactic inferior vena cava filter placement. Recurrent bouts of renal stones prompted serial CT imaging in 2004. In this brief report, we describe erosion and ossification of the L3 vertebral body by a Greenfield filter strut.

  4. A periodic network of neurochemical modules in the inferior colliculus.

    PubMed

    Chernock, Michelle L; Larue, David T; Winer, Jeffery A

    2004-02-01

    A new organization has been found in shell nuclei of rat inferior colliculus. Chemically specific modules with a periodic distribution fill about half of layer 2 of external cortex and dorsal cortex. Modules contain clusters of small glutamic acid decarboxylase-positive neurons and large boutons at higher density than in other inferior colliculus subdivisions. The modules are also present in tissue stained for parvalbumin, cytochrome oxidase, nicotinamide adenine dinucleotide phosphate-diaphorase, and acetylcholinesterase. Six to seven bilaterally symmetrical modules extend from the caudal extremity of the external cortex of the inferior colliculus to its rostral pole. Modules are from approximately 800 to 2200 microm long and have areas between 5000 and 40,000 microm2. Modules alternate with immunonegative regions. Similar modules are found in inbred and outbred strains of rat, and in both males and females. They are absent in mouse, squirrel, cat, bat, macaque monkey, and barn owl. Modules are immunonegative for glycine, calbindin, serotonin, and choline acetyltransferase. The auditory cortex and ipsi- and contralateral inferior colliculi project to the external cortex. Somatic sensory influences from the dorsal column nuclei and spinal trigeminal nucleus are the primary ascending sensory input to the external cortex; ascending auditory input to layer 2 is sparse. If the immunopositive modular neurons receive this input, the external cortex could participate in spatial orientation and somatic motor control through its intrinsic and extrinsic projections. PMID:14759566

  5. Inferior Colliculus Lesions Impair Eyeblink Conditioning in Rats

    ERIC Educational Resources Information Center

    Freeman, John H.; Halverson, Hunter E.; Hubbard, Erin M.

    2007-01-01

    The neural plasticity necessary for acquisition and retention of eyeblink conditioning has been localized to the cerebellum. However, the sources of sensory input to the cerebellum that are necessary for establishing learning-related plasticity have not been identified completely. The inferior colliculus may be a source of sensory input to the…

  6. How much does inferior capsular shift reduce shoulder volume?

    PubMed

    Lubowitz, J; Bartolozzi, A; Rubinstein, D; Ciccotti, M; Schweitzer, M; Nazarian, L; Lombardi, J; Dellose, S; Landsdorf, A; Miller, L

    1996-07-01

    The purpose of this study was to quantitate the effect of inferior capsular shift on shoulder volume. Four fresh frozen cadaveric shoulders were analyzed. Volume before and after shift was determined using 3 techniques: (1) Magnetic resonance imaging sequences were digitized to computer and analyzed for volume via a 35-mm camera using Cue 2 software. The capsule was delineated by contrast between light and dark regions. Volume was calculated by summing the total area of respective slices. (2) Ultrasound images, obtained after surgical exposure of the capsule, were digitized. Volume was calculated using the formula for a prolate ellipsoid. (3) An 18-gauge needle was used to inject and evacuate saline via an anterior approach. Quantity of aspirated fluid provided a direct measure of volume. Inferior capsular shift was performed. After the operation, measurements were repeated. Inferior capsular shift reduced volume in all shoulders with each technique. On average, inferior capsular shift reduced joint volume by 57 %). A measurable reduction in shoulder joint volume is an effect of capsular shift. This measurement may have clinical application if volume is an indicator of instability or laxity. PMID:8653983

  7. Duodenal perforation caused by an inferior vena cava filter.

    PubMed

    Bae, Mi Ju; Chung, Sung Woon; Lee, Chung Won; Kim, Sangpil; Song, Seunghwan

    2012-02-01

    The inferior vena cava (IVC) filter is known as an effective and safe method for preventing fatal pulmonary thromboembolism in patients with deep vein thrombosis. Usually, the remaining IVC filters are asymptomatic and do not cause clinical problems. We report a case of duodenal perforation caused by a remaining IVC filter. PMID:22363914

  8. Traumatic longitudinal splitting of the inferior rectus muscle.

    PubMed

    Laursen, Jessica; Demer, Joseph L

    2011-04-01

    Orbital floor fractures and associated injuries can cause strabismus. We present the case of a 34-year-old man with incomitant strabismus after orbital reconstruction following a high-impact baseball injury. Multipositional, high-resolution magnetic resonance imaging revealed extensive longitudinal splitting of the inferior rectus muscle by an orbital floor implant that separated its orbital and global layers. PMID:21463958

  9. Sinus bradycardia as a predictor of right coronary artery occlusion in patients with inferior myocardial infarction.

    PubMed

    Serrano, C V; Bortolotto, L A; César, L A; Solimene, M C; Mansur, A P; Nicolau, J C; Ramires, J A

    1999-01-01

    Differentiation of right coronary artery (RCA) from left circumflex artery (LCxA) occlusion may be difficult since both can present an electrocardiographic pattern of inferior myocardial infarction (IMI). We studied 133 patients with IMI, 92 patients with RCA occlusion and 41 patients with LCxA occlusion. Risk factors such as previous MI, arterial hypertension, diabetes, smoking, and dislipemia, were similar for RCA and LCxA occlusions. Patients with RCA occlusion had a higher incidence of isolated IMI than patients with LCxA occlusion, 50% vs. 17%, respectively (P<0.001). Arterial hypotension was more prevalent (P<0.05) among patients with RCA (18%) rather than those with LCxA occlusion (2%). RCA occlusion presented an association with sinus bradycardia, an association not observed with LCxA occlusion (15% vs. 0%, respectively; P<0.01). Total atrioventricular block was only present among patients with RCA (18%). Proximal occlusions of the RCA presented lower heart rates (sinus bradycardia) than medial and distal occlusions (13% vs. 1% and 1%, respectively; P<0.0001 and P<0.001). Therefore, regarding patients with IMI: (1) sinus bradycardia is more frequent when the infarct-related artery is the RCA; (2) proximal occlusions of the right coronary predispose low heart rates; and (3) occlusion of the LCxA rarely induces sinus bradycardia. PMID:10077404

  10. Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

    PubMed Central

    Meister, Rebecca E; Weber, Tania; Princip, Mary; Schnyder, Ulrich; Barth, Jürgen; Znoj, Hansjörg; Schmid, Jean-Paul; von Känel, Roland

    2015-01-01

    Objectives Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. Methods We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. Results Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=−0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=−0.05, p<0.05) and arousal (b=−0.09, p<0.05), but not with dissociation and avoidance. Conclusions The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support. PMID:26568834

  11. Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter.

    PubMed

    Rich, Michael E; Tseng, Andrew; Lim, Hae W; Wang, Paul J; Su, Wilber W

    2015-01-01

    The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) - the atrial septum's thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P <0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a "cryoballoon only" technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures. PMID:26132435

  12. Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

    PubMed Central

    Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.

    2011-01-01

    Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients

  13. Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.

    PubMed

    Calura, Enrica; Bisognin, Andrea; Manzoni, Martina; Todoerti, Katia; Taiana, Elisa; Sales, Gabriele; Morgan, Gareth J; Tonon, Giovanni; Amodio, Nicola; Tassone, Pierfrancesco; Neri, Antonino; Agnelli, Luca; Romualdi, Chiara; Bortoluzzi, Stefania

    2016-01-19

    The identification of overexpressed miRNAs in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. miRNA and gene expression profiles of two large representative MM datasets, available from retrospective and prospective series and encompassing a total of 249 patients at diagnosis, were analyzed by means of in silico integrative genomics methods, based on MAGIA2 and Micrographite computational procedures. We first identified relevant miRNA/transcription factors/target gene regulation circuits in the disease and linked them to biological processes. Members of the miR-99b/let-7e/miR-125a cluster, or of its paralog, upregulated in t(4;14), were connected with the specific transcription factors PBX1 and CEBPA and several target genes. These results were validated in two additional independent plasma cell tumor datasets. Then, we reconstructed a non-redundant miRNA-gene regulatory network in MM, linking miRNAs, such as let-7g, miR-19a, mirR-20a, mir-21, miR-29 family, miR-34 family, miR-125b, miR-155, miR-221 to pathways associated with MM subtypes, in particular the ErbB, the Hippo, and the Acute myeloid leukemia associated pathways. PMID:26496024

  14. Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients

    PubMed Central

    Manzoni, Martina; Todoerti, Katia; Taiana, Elisa; Sales, Gabriele; Morgan, Gareth J.; Tonon, Giovanni; Amodio, Nicola; Tassone, Pierfrancesco; Neri, Antonino; Agnelli, Luca; Romualdi, Chiara; Bortoluzzi, Stefania

    2016-01-01

    The identification of overexpressed miRNAs in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. miRNA and gene expression profiles of two large representative MM datasets, available from retrospective and prospective series and encompassing a total of 249 patients at diagnosis, were analyzed by means of in silico integrative genomics methods, based on MAGIA2 and Micrographite computational procedures. We first identified relevant miRNA/transcription factors/target gene regulation circuits in the disease and linked them to biological processes. Members of the miR-99b/let-7e/miR-125a cluster, or of its paralog, upregulated in t(4;14), were connected with the specific transcription factors PBX1 and CEBPA and several target genes. These results were validated in two additional independent plasma cell tumor datasets. Then, we reconstructed a non-redundant miRNA-gene regulatory network in MM, linking miRNAs, such as let-7g, miR-19a, mirR-20a, mir-21, miR-29 family, miR-34 family, miR-125b, miR-155, miR-221 to pathways associated with MM subtypes, in particular the ErbB, the Hippo, and the Acute myeloid leukemia associated pathways. PMID:26496024

  15. miRNAs in brain development

    SciTech Connect

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.

  16. miRegulome: a knowledge-base of miRNA regulomics and analysis

    PubMed Central

    Barh, Debmalya; Kamapantula, Bhanu; Jain, Neha; Nalluri, Joseph; Bhattacharya, Antaripa; Juneja, Lucky; Barve, Neha; Tiwari, Sandeep; Miyoshi, Anderson; Azevedo, Vasco; Blum, Kenneth; Kumar, Anil; Silva, Artur; Ghosh, Preetam

    2015-01-01

    miRNAs regulate post transcriptional gene expression by targeting multiple mRNAs and hence can modulate multiple signalling pathways, biological processes, and patho-physiologies. Therefore, understanding of miRNA regulatory networks is essential in order to modulate the functions of a miRNA. The focus of several existing databases is to provide information on specific aspects of miRNA regulation. However, an integrated resource on the miRNA regulome is currently not available to facilitate the exploration and understanding of miRNA regulomics. miRegulome attempts to bridge this gap. The current version of miRegulome v1.0 provides details on the entire regulatory modules of miRNAs altered in response to chemical treatments and transcription factors, based on validated data manually curated from published literature. Modules of miRegulome (upstream regulators, downstream targets, miRNA regulated pathways, functions, diseases, etc) are hyperlinked to an appropriate external resource and are displayed visually to provide a comprehensive understanding. Four analysis tools are incorporated to identify relationships among different modules based on user specified datasets. miRegulome and its tools are helpful in understanding the biology of miRNAs and will also facilitate the discovery of biomarkers and therapeutics. With added features in upcoming releases, miRegulome will be an essential resource to the scientific community. Availability: http://bnet.egr.vcu.edu/miRegulome. PMID:26243198

  17. Liver cirrhosis in hepatic vena cava syndrome (or membranous obstruction of inferior vena cava)

    PubMed Central

    Shrestha, Santosh Man

    2015-01-01

    Hepatic vena cava syndrome (HVCS) also known as membranous obstruction of inferior vena cava reported mainly from Asia and Africa is an important cause of hepatic venous outflow obstruction (HVOO) that is complicated by high incidence of liver cirrhosis (LC) and moderate to high incidence of hepatocellular carcinoma (HCC). In the past the disease was considered congenital and was included under Budd-Chiari syndrome (BCS). HVCS is a chronic disease common in developing countries, the onset of which is related to poor hygienic living condition. The initial lesion in the disease is a bacterial infection induced localized thrombophlebitis in hepatic portion of inferior vena cava at the site where hepatic veins open which on resolution transforms into stenosis, membrane or thick obstruction, and is followed by development of cavo-caval collateral anastomosis. The disease is characterized by long asymptomatic period and recurrent acute exacerbations (AE) precipitated by clinical or subclinical bacterial infection. AE is managed with prolonged oral antibiotic. Development of LC and HCC in HVCS is related to the severity and frequency of AEs and not to the duration of the disease or the type or severity of the caval obstruction. HVOO that develops during severe acute stage or AE is a pre-cirrhotic condition. Primary BCS on the other hand is a rare disease related to prothrombotic disorders reported mainly among Caucasians that clinically manifest as acute, subacute disease or as fulminant hepatic failure; and is managed with life-long anticoagulation, porto-systemic shunt/endovascular angioplasty and stent or liver transplantation. As epidemiology, etiology and natural history of HVCS are different from classical BCS, it is here, recognized as a separate disease entity, a third primary cause of HVOO after sinusoidal obstruction syndrome and BCS. Understanding of the natural history has made early diagnosis of HVCS possible. This paper describes epidemiology, natural

  18. miRNA Digger: a comprehensive pipeline for genome-wide novel miRNA mining.

    PubMed

    Yu, Lan; Shao, Chaogang; Ye, Xinghuo; Meng, Yijun; Zhou, Yincong; Chen, Ming

    2016-01-01

    MicroRNAs (miRNAs) are important regulators of gene expression. The recent advances in high-throughput sequencing (HTS) technique have greatly facilitated large-scale detection of the miRNAs. However, thoroughly discovery of novel miRNAs from the available HTS data sets remains a major challenge. In this study, we observed that Dicer-mediated cleavage sites for the processing of the miRNA precursors could be mapped by using degradome sequencing data in both animals and plants. In this regard, a novel tool, miRNA Digger, was developed for systematical discovery of miRNA candidates through genome-wide screening of cleavage signals based on degradome sequencing data. To test its sensitivity and reliability, miRNA Digger was applied to discover miRNAs from four organs of Arabidopsis. The results revealed that a majority of already known mature miRNAs along with their miRNA*s expressed in these four organs were successfully recovered. Notably, a total of 30 novel miRNA-miRNA* pairs that have not been registered in miRBase were discovered by miRNA Digger. After target prediction and degradome sequencing data-based validation, eleven miRNA-target interactions involving six of the novel miRNAs were identified. Taken together, miRNA Digger could be applied for sensitive detection of novel miRNAs and it could be freely downloaded from http://www.bioinfolab.cn/miRNA_Digger/index.html. PMID:26732371

  19. miRNome Analysis of CML Cells.

    PubMed

    Yang, Yadong; Ding, Nan; Dong, Xunong; Fang, Xiangdong

    2016-01-01

    Next-generation sequencing technologies have greatly accelerated the biological and medical progression. As one of the applications, miRNA-Seq is invaluable in detecting and characterizing genome-wide miRNAs of either too high or too low abundance. Besides, it can also be used in detecting novel miRNAs. Here, we describe an ab initio analysis of an example chronic myeloid leukemia miRNA sequencing data set to quantify the global expression of miRNAs, detect differential expression and novel miRNAs, and predict target genes. The run time of this protocol may vary depending on the volume of miRNA sequencing data and available computing resources but takes ~5 h of computing time for typical experiments and less than 1 h of hands-on time. PMID:27581150

  20. Αcute Exercise Alters the Levels of Human Saliva miRNAs Involved in Lipid Metabolism.

    PubMed

    Konstantinidou, A; Mougios, V; Sidossis, L S

    2016-06-01

    The response of micro-ribonucleic acid (miRNA) expression to exercise has not been studied in saliva, although saliva combines non-invasive collection with the largest number of miRNA species among biological fluids and tissues. Thus, the purpose of this study was to investigate the effect of acute exercise on the expression of 8 human saliva miRNAs involved in lipid metabolism. 19 healthy, physically active men (VO2max, 40.9±1.6 mL·kg(-1)·min(-1), mean±se) performed a 50-min interval exercise program on stationary bicycle (spinning). Saliva samples were collected before and after exercise for miRNA expression analysis by real-time polymerase chain reaction. Statistically significant (p<0.05) changes after exercise were found in 2 of the 8 miRNAs, namely, hsa-miR-33a (fold change, 7.66±2.94; p=0.012), which regulates cholesterol homeostasis and fatty acid metabolism in the liver, and hsa-miR-378a (fold change 0.79±0.11, p=0.048), which regulates energy homeostasis and affects lipogenesis and adipogenesis. These alterations may contribute to our understanding of physiological responses to exercise and the therapeutic potential of exercise against cardiovascular disease, obesity, and the metabolic syndrome. Moreover, our findings open the possibility of noninvasively studying miRNAs that regulate the function of specific organs. PMID:27116339

  1. MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1.

    PubMed

    He, Wangwei; Huang, He; Xie, Qiang; Wang, Zhiqiang; Fan, Yang; Kong, Bin; Huang, Dan; Xiao, Yali

    2016-07-01

    Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling. PMID:26589288

  2. Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients

    PubMed Central

    Barry, Simone E; Chan, Brian; Ellis, Magda; Yang, YuRong; Plit, Marshall L; Guan, Guangyu; Wang, Xiaolin; Britton, Warwick J; Saunders, Bernadette M

    2015-01-01

    Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population. PMID:25753045

  3. Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients.

    PubMed

    Barry, Simone E; Chan, Brian; Ellis, Magda; Yang, YuRong; Plit, Marshall L; Guan, Guangyu; Wang, Xiaolin; Britton, Warwick J; Saunders, Bernadette M

    2015-07-01

    Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population. PMID:25753045

  4. Deep Vein Thrombosis Provoked by Inferior Vena Cava Agenesis.

    PubMed

    Haddad, Raad A; Saadaldin, Mazin; Kumar, Binay; Bachuwa, Ghassan

    2015-01-01

    Inferior vena cava agenesis (IVCA) is a rare congenital anomaly that can be asymptomatic or present with vague, nonspecific symptoms, such as abdominal or lower back pain, or deep vein thrombosis (DVT). Here, we present a 55-year-old male who came with painless swelling and redness of his left lower limb. On examination, swelling and redness were noted extending from the left foot to the upper thigh; it was also warm compared to his right lower limb. Venous Doppler ultrasound was done which showed DVT extending up to the common femoral vein. Subsequently, computed-tomography (CT) of the chest and abdomen was done to exclude malignancy or venous flow obstruction; it revealed congenital absence (agenesis) of the infrarenal inferior vena cava (IVC). PMID:26788400

  5. Isolated inferior rectus muscle rupture after blunt orbital trauma

    PubMed Central

    Tomasetti, Patrick; Metzler, Philipp; Jacobsen, Christine

    2013-01-01

    A 44-year-old man was referred to our department with diplopia, periorbital swelling and haematoma of the left eye after orbital trauma due to a punch. During the examination, mild enophthalmos, hypertropia and a total absence of infraduction were observed. An orbital computed tomography (CT) scan demonstrated a left orbital floor blow-out fracture, with caudal herniation of periorbital fat and rectus inferior muscle. Repair was performed under total anaesthesia with placement of a Titan mesh. The following days were marked by the persistence of diplopia without improvement of infraduction. A postoperative, 0.5 mm CT scan highlighted a complete rupture of the inferior rectus muscle, not seen before operation, by a 1.0 mm-sliced CT. In this case, orthoptic therapy was undertaken with good results after 6 months and without need of a second repair. PMID:24963904

  6. Ruptured Total Intrameatal Anterior Inferior Cerebellar Artery Aneurysm

    PubMed Central

    Kim, Hyung Cheol; Chang, In Bok; Lee, Ho Kook

    2015-01-01

    Among the distal anterior inferior cerebellar artery (AICA) aneurysms, a unique aneurysm at the meatal loop inside the internal auditory meatus is extremely rare. The authors report a case of surgically treated total intrameatal AICA aneurysm. A 62-year-old female patient presenting with sudden bursting headache and neck pain was transferred to our department. Computed tomography and digital subtraction angiography showed subarachnoid hemorrhage at the basal, prepontine cistern and an aneurysm of the distal anterior inferior cerebellar artery inside the internal auditory meatus. Surgery was performed by retrosigmoid craniotomy with unroofing of the internal auditory meatus. The aneurysm was identified between the seventh and eighth cranial nerve in the meatus and was removed from the canal and clipped with a small straight Sugita clip. After operation the patient experienced transient facial paresis and tinnitus but improved during follow up. PMID:26361531

  7. Pheochromocytoma with inferior vena cava thrombosis: An unusual association

    PubMed Central

    Kota, Sunil K.; Kota, Siva K.; Jammula, Sruti; Meher, Lalit K.; Modi, Kirtikumar D.

    2012-01-01

    Pheochromocytomas have been described in association with vascular abnormalities like renal artery stenosis. A 48-year-old man was admitted to our hospital with the complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and hypertension. For last several days, he was having a dull aching abdominal pain. Abdominal computed tomography (CT) revealed the presence of a left adrenal pheochromocytoma. An inferior vena cava (IVC) venogram via the right jugular vein demonstrated occlusion of the IVC inferior to the right atrium. Surgical removal of pheochromocytoma was done, followed by anticoagulant treatment for IVC thrombosis, initially with subcutaneous low molecular weight heparin, and then with oral warfarin, resulting in restoration of patency. To the best of our knowledge, the occurrence of pheochromocytoma in IVC thrombosis has not been reported so far from India. Possible mechanisms of such an involvement are discussed. PMID:22629039

  8. Inferior vena cava injury repair, a successful outcome.

    PubMed

    Adhikary, S; Shakya, V C; Dhungel, K; Rajbanshi, S; Shakya, V; Khaniya, S; Maskey, P

    2012-03-01

    Inferior ver a cava (IVC) injuries are very very infrequent; yet it still happens to be the most frequently injured retroperitoneal vascular structure. Fifty percent of the patients can't even make it to the hospital. Even when half of them manage to attend the hospital the mortality rates for the great vessel injury are still very high perhaps due to the low index of suspicion, delayed or inadequate volume resuscitation, difficulty in diagnosis and also due to some technical problems associated in its repair. We present a young male with an abdominal stab injury who had a near transected inferior vena cava at operation. Aggressive perioperative management and the correct judgement by our team at the right time possibly made the patient survive. The rarity of this condition and a review of the literature with some discussion are presented. PMID:23441500

  9. miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target

    PubMed Central

    Yamamoto, Haruna; Lu, Jun; Oba, Shigeyoshi; Kawamata, Toyotaka; Yoshimi, Akihide; Kurosaki, Natsumi; Yokoyama, Kazuaki; Matsushita, Hiromichi; Kurokawa, Mineo; Tojo, Arinobu; Ando, Kiyoshi; Morishita, Kazuhiro; Katagiri, Koko; Kotani, Ai

    2016-01-01

    The Ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is located on chromosome 3q26, over-expression in some acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Elevated Evi1 expression in AML is associated with unfavorable prognosis. Therefore, Evi1 is one of the strong candidate in molecular target therapy for the leukemia. MicroRNAs (miRNAs) are small non-coding RNAs, vital to many cell functions that negatively regulate gene expression by translation or inducing sequence-specific degradation of target mRNAs. As a novel biologics, miRNAs is a promising therapeutic target due to its low toxicity and low cost. We screened miRNAs which down-regulate Evi1. miR-133 was identified to directly bind to Evi1 to regulate it. miR-133 increases drug sensitivity specifically in Evi1 expressing leukemic cells, but not in Evi1-non-expressing cells The results suggest that miR-133 can be promising therapeutic target for the Evi1 dysregulated poor prognostic leukemia. PMID:26754824

  10. Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue.

    PubMed

    Lai, C-Y; Lee, S-Y; Scarr, E; Yu, Y-H; Lin, Y-T; Liu, C-M; Hwang, T-J; Hsieh, M H; Liu, C-C; Chien, Y-L; Udawela, M; Gibbons, A S; Everall, I P; Hwu, H-G; Dean, B; Chen, W J

    2016-01-01

    Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia. PMID:26784971

  11. Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke.

    PubMed

    Choi, Gun Ho; Ko, Ki Han; Kim, Jung Oh; Kim, Jinkwon; Oh, Seung Hun; Han, In Bo; Cho, Kyung Gi; Kim, Ok Joon; Bae, Jinkun; Kim, Nam Keun

    2016-07-01

    MicroRNAs (miRNAs or miRs) are small (19-23 nt) non-coding RNA molecules that are endogenous regulators of gene expression. Previous studies have found that some miRNAs are related to the progression of ischemia in the cerebral artery. Furthermore, a recent study found a significant association between miRNA single nucleotide polymorphisms (SNPs) and the risk of ischemic stroke. Therefore, it may be valuable to investigate associations between megakaryocyte formation-related miRNA polymorphisms and the prevalence of ischemic stroke. We thus conducted a case-control study of 1,000 individuals who were screened for 4 miRNA polymorphisms (miR‑34a rs6577555C>A, miR-130a rs731384C>T, miR-150 rs73056059G>A and miR‑155 rs767649T>A) by PCR-RFLP analysis. The study population comprised 596 patients with ischemic stroke and 404 control subjects without any history of neurological disorders. We observed associations between miRNA polymorphisms and individual stroke subtypes. The miR‑150 polymorphisms were significantly associated with ischemic stroke subgroups, such as left anterior descending artery (LAD) disease [GG vs. AA: adjusted odds ratio (AOR), 1.922; 95% confidence interval (CI), 1.003-3.681] and cardioembolism (GG vs. AA: AOR, 2.996; 95% CI, 1.293-6.939). Additionally, Cox proportional analysis indicated that the miR‑150GA genotype was associated with survival in patients with ischemic stroke [adjusted hazard ratio (HR), 2.063; 95% CI, 1.142-3.727; P=0.017] and with the LAD subgroup [adjusted HR, 3.021; 95% CI, 1.345-6.785; P=0.008]. Our findings suggest that miR‑150 polymorphisms may contribute to the development of ischemic stroke and may potentially act as biomarkers to predict the risk of ischemic stroke. To the best of our knowledge, this is the first study to evaluate the association between miRNA polymorphisms (miR-34aC>A, miR-130aC>T, miR-150G>A and miR-155T>A) and ischemic stroke. PMID:27246008

  12. Fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve).

    PubMed

    Zeng, Rong; Frederick-Dyer, Katherine; Ferguson, N Lynn; Lewis, James; Fu, Yitong

    2012-09-01

    Fibrolipomatous hamartoma (FLH) is a rare, benign lesion of the peripheral nerves most frequently involving the median nerve and its digital branches (80 %). Pathognomonic MR features of FLH such as coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes have been described by Marom and Helms, obviating the need for diagnostic biopsy. We present a case of fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve) with associated subcutaneous fat proliferation. PMID:22526881

  13. Use of Prophylactic Inferior Vena Cava Filters in Trauma

    PubMed Central

    Naiem, Ahmed A.; Al-Hinai, Alreem K.; Al-Sukaiti, Rashid; Al-Qadhi, Hani

    2016-01-01

    Venous thromboembolisms, specifically pulmonary embolisms (PEs), represent a significant burden on healthcare systems worldwide, particularly within the setting of trauma. According to the literature, PEs are the most common cause of in-hospital death; however, this condition can be prevented with a variety of prophylactic and therapeutic measures. This article aimed to examine current evidence on the use, indications for prophylaxis, outcomes and complications of prophylactic inferior vena cava filters in trauma patients. PMID:26909219

  14. Gaining Surgical Access for Repositioning the Inferior Alveolar Neurovascular Bundle

    PubMed Central

    Al-Siweedi, Saif Yousif Abdullah; Nambiar, P.; Shanmuhasuntharam, P.; Ngeow, W. C.

    2014-01-01

    This study is aimed at determining anatomical landmarks that can be used to gain access to the inferior alveolar neurovascular (IAN) bundle. Scanned CBCT (i-CAT machine) data of sixty patients and reconstructions performed using the SimPlant dental implant software were reviewed. Outcome variables were the linear distances of the mandibular canal to the inferior border and the buccal cortex of the mandible, measured immediately at the mental foramen (D1) and at 10, 20, 30, and 40 mm (D2–D5) distal to it. Predictor variables were age, ethnicity, and gender of subjects. Apicobasal assessment of the canal reveals that it is curving downward towards the inferior mandibular border until 20 mm (D3) distal to the mental foramen where it then curves upwards, making an elliptic-arc curve. The mandibular canal also forms a buccolingually oriented elliptic arc in relation to the buccal cortex. Variations due to age, ethnicity, and gender were evident and this study provides an accurate anatomic zone for gaining surgical access to the IAN bundle. The findings indicate that the buccal cortex-IAN distance was greatest at D3. Therefore, sites between D2 and D5 can be used as favorable landmarks to access the IAN bundle with the least complications to the patient. PMID:24892077

  15. Combination-sensitive neurons in the inferior colliculus.

    PubMed

    Mittmann, D H; Wenstrup, J J

    1995-10-01

    We examined whether neurons in the inferior colliculus of the mustached bat (Pteronotus parnellii) are combination sensitive, responding to both low- and high-frequency components of the bat's sonar signal. These neurons, previously reported in the thalamus and cortex, analyze sonar target features including distance. Of 82 single units and 36 multiple units from the 58-112 kHz representations of the inferior colliculus, most (86%) displayed sensitivity to low-frequency sounds that was tuned in the range of the fundamental biosonar component (24-31 kHz). All histologically localized units were in the central nucleus of the inferior colliculus (ICC). There were two major types of combination-sensitive influences. Many neurons were facilitated by low-frequency sounds and selective for particular delays between the low- and high-frequency components. In other neurons, the low-frequency signal was inhibitory if presented simultaneously or a few milliseconds prior to the high-frequency signal. The results indicate that mechanisms creating specialized frequency comparisons and delay sensitivity in combination-sensitive neurons operate at the ICC or below. Since combination sensitivity or multipeaked tuning curves occur in the auditory systems of many species, ICC neurons in these animals may also respond to species-specific frequency combinations. PMID:8974996

  16. Acute arrhythmogenesis after myocardial infarction in normotensive rats: influence of high salt intake.

    PubMed

    Baldo, Marcelo Perim; Teixeira, Anna Késia Guerrat; Rodrigues, Sérgio Lamêgo; Mill, José Geraldo

    2012-03-01

    A high salt diet is a known risk factor for cardiovascular diseases that leads to cardiac hypertrophy and creates a substrate for arrhythmias and sudden death. However, acute arrhythmogenesis after infarction has not been studied. Male Wistar rats (21 days) received drinking water (MI) or 1% NaCl solution (MI-Salt-C) for 4 weeks. Water was given to another group for 4 weeks, and on the day before surgery, animals received a 1% NaCl solution (MI-Salt-A). Non-invasive systolic blood pressure (SBP) was obtained before surgery. Myocardial infarction (MI) was produced by permanent occlusion of the left coronary artery. Electrocardiogram was monitored during the first 30 min post-occlusion to evaluate arrhythmias. Although SBP was not altered by salt intake (SHAM: 114±2, MI: 112±2, MI-Salt-C: 115±2, MI-Salt-A: 116±4 mm Hg), ventricular hypertrophy was observed in the animals receiving chronic salt diet (SHAM: 0.22±0.008, MI: 0.23±0.007, MI-Salt-C: 0.28±0.01; MI-Salt-A: 0.23±0.01 g/cm; P<0.05). Ventricular premature beats increased in both salt-loaded groups compared to MI group (MI: 805±81, MI-Salt-C: 1145±98; MI-Salt-A: 1023±77; P<0.05). Atrioventricular blockade was only observed in animals subjected to high salt intake (MI-Salt-C: 38.9%; MI-Salt-A: 42.1%). High salt intake was associated with increased post-infarct arrhythmias; however, this effect was unrelated to ventricular hypertrophy. PMID:22142697

  17. Mandibular osteotomies after drawing out the inferior alveolar nerve along the canal.

    PubMed

    Jin, Hoon; Kim, Byung-Gun

    2003-01-01

    In some cases, the inferior alveolar nerve runs through a lower course than usual. In such cases, osteotomy of the mandible can injure the inferior alveolar nerves. In other instances, the course of the mandibular osteotomy can meet that of the inferior alveolar nerve. In these cases, a useful method may be excavating the canal and drawing the nerve out through it. With this technique, we can make the osteotomy as initially planned with minimal damage to the inferior alveolar nerve. PMID:14629066

  18. Assessment of serum prolactin levels in acute myocardial infarction: The role of pharmacotherapy

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Awad, Mohamed S.; Alrifai, Sinan B.

    2016-01-01

    Background: Hyperprolactinemia may reflect neuroendocrine stress reaction against acute coronary syndromes. Aim: The aim of the present study was evaluation of the serum prolactin level in the acute myocardial infarction (MI) regarding the current pharmacotherapy in management of MI. Setting and Design: Cross-sectional clinical based study. Subjects and Methods: This cross-sectional clinical study involved all patients with acute MI in a coronary care unit, a total number of 44 patients (45% males and 55% females) with age ranged from 40 to 75 years. A full history for modifiable risk factors and current therapy with aspirin, clopidogrel and or metformin, all patients are nonsmokers. The anthropometric measurements; for estimations of body mass index (kg/m2), electrocardiography was obtained. Fasting blood samples were taken in the morning from all patients and the sera used for estimations of routine investigation and determination of ischemic cardiac biomarkers like cardiac troponin I (cTnI) and serum prolactin level. Results: This study shows a significant increase in the serum prolactin in acute MI as compared with the control. In acute MI serum cTnI elevation was correlated with serum prolactin increments. In metformin-treated group, there was a lowest prolactin serum level. Conclusions: Serum prolactin level increased in acute MI, and positively correlated with cardiac troponin level and reflects underlying cardiovascular complications. PMID:26904472

  19. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  20. An Unusual Case Of Inferior Turbinate Osteoma Removed Endoscopically: A Case Report.

    PubMed

    Prasad, Shyamakant; Kumar, Ashok; Naik, Sulabha M; Kalhan, Shivani

    2016-03-01

    Inferior turbinate osteoma is exceptionally rare. Here we are reporting a case of inferior turbinate osteoma presented with history of left nasal obstruction. CT unveiled osseous hypertrophy of left inferior turbinate. Osteoma was removed endoscopically using hammer and gouge. This is the fourth case to be reported in the world literature and second in India. PMID:27066424

  1. 75 FR 9228 - Draft Guidance for Industry on Non-Inferiority Clinical Trials; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Non-Inferiority Clinical... ``Non- Inferiority Clinical Trials.'' This draft guidance provides sponsors and review staff in the... announcing the availability of a draft guidance for industry entitled ``Non-Inferiority Clinical...

  2. So, Why Sol-Mi? American Music Education

    ERIC Educational Resources Information Center

    Bennett, Peggy D.

    2005-01-01

    Walk into any primary grade music class in the U.S., and you will likely hear teacher and students singing a musical greeting, such as "Good morning boys and girls" (sol-mi-mi-sol-sol-mi) and the response "Good morning Miss Purdy" (sol-mi-mi-sol-mi-mi). Since about the 1970s, teachers have been beginning and ending music class for young children…

  3. miRNA-based drought regulation in wheat.

    PubMed

    Akdogan, Guray; Tufekci, Ebru Derelli; Uranbey, Serkan; Unver, Turgay

    2016-05-01

    MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. Drought is a common environmental stress influencing crop growth and development. To date, it has been reported that a number of plant miRNA are involved in drought stress response. In this study, we comparatively investigated drought stress-responsive miRNAs in the root and leaf of bread wheat (Triticum aestivum cv. Sivas 111/33) by miRNA microarray screening. miRNA microarray analysis showed that 285 miRNAs (207 upregulated and 78 downregulated) and 244 miRNAs (115 upregulated and 129 downregulated) were differentially expressed in leaf and root tissues, respectively. Among the differentially expressed miRNAs, 23 miRNAs were only expressed in the leaf and 26 miRNAs were only expressed in the root of wheat growth under drought stress. Upon drought treatment, expression of miR159, miR160, miR166, miR169, miR172, miR395, miR396, miR408, miR472, miR477, miR482, miR1858, miR2118, and miR5049 were found to be significantly differentiated in bread wheat. The regulatory network analysis showed that miR395 has connections with a number of target transcripts, and miR159 and miR319 share a number of target genes. Drought-tolerant and drought-sensitive wheat cultivars showed altered expression pattern upon drought stress in terms of investigated miRNA and their target transcript expression level. PMID:26141043

  4. miR-340 suppresses glioblastoma multiforme.

    PubMed

    Huang, Daquan; Qiu, Shuwei; Ge, Ruiguang; He, Lei; Li, Mei; Li, Yi; Peng, Ying

    2015-04-20

    Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM. PMID:25831237

  5. miRNA and Vascular Cell Movement

    PubMed Central

    Yue, Junming

    2011-01-01

    miRNAs are a new class of endogenous small RNAs that negatively regulate gene expression at the posttranscriptional level. Accumulating experimental evidence shows that miRNAs regulate cellular apoptosis, proliferation, differentiation, and migration. Dysregulation of miRNA expression leads to various human diseases including cancer and cardiovascular disease. miRNA maturation is regulated at multiple steps by different mechanisms, including miRNA editing, hairpin loop binding, self-regulation, and cross-talk with other signaling pathways. Vascular cell movement plays a pivotal role in the development of various cancers and cardiovascular diseases. miRNAs have been found to regulate vascular cell movement. Presently the chemically synthesized antagomir, miRNA mimics have been widely used in investigating the biological functions of miRNA genes. The viral vectors, including adenoviral, lentiviral, and adeno-associated viral vectors, have been used to efficiently overexpress or knockdown miRNAs in vitro and in vivo. Therefore, targeting vascular cell movement using miRNA-based drug or gene therapy would provide a novel therapeutic approach in the treatment of cancers and vascular diseases. PMID:21241758

  6. Migrated Disc at Cervicothoracic Junction Presenting as Acute Paraplegia

    PubMed Central

    Mahore, Amit; Agarwal, Monit; Tikeykar, Vishakha

    2015-01-01

    Herein, we report on an inferior migration of an intervertebral disc C6-7 to the cervicothoracic junction manifesting as acute paraplegia. The patient showed a remarkable recovery after the surgery. The diagnostic dilemma and management difficulties of such an entity are briefly discussed. PMID:26097662

  7. Migrated Disc at Cervicothoracic Junction Presenting as Acute Paraplegia.

    PubMed

    Mahore, Amit; Agarwal, Monit; Ramdasi, Raghvendra; Tikeykar, Vishakha

    2015-06-01

    Herein, we report on an inferior migration of an intervertebral disc C6-7 to the cervicothoracic junction manifesting as acute paraplegia. The patient showed a remarkable recovery after the surgery. The diagnostic dilemma and management difficulties of such an entity are briefly discussed. PMID:26097662

  8. Ionizing Radiation–Inducible miR-27b Suppresses Leukemia Proliferation via Targeting Cyclin A2

    SciTech Connect

    Wang, Bo; Li, Dongping; Kovalchuk, Anna; Litvinov, Dmitry; Kovalchuk, Olga

    2014-09-01

    Purpose: Ionizing radiation is a common carcinogen that is important for the development of leukemia. However, the underlying epigenetic mechanisms remain largely unknown. The goal of the study was to explore microRNAome alterations induced by ionizing radiation (IR) in murine thymus, and to determine the role of IR-inducible microRNA (miRNA/miR) in the development of leukemia. Methods and Materials: We used the well-established C57BL/6 mouse model and miRNA microarray profiling to identify miRNAs that are differentially expressed in murine thymus in response to irradiation. TIB152 human leukemia cell line was used to determine the role of estrogen receptor–α (ERα) in miR-27b transcription. The biological effects of ectopic miR-27b on leukemogenesis were measured by western immunoblotting, cell viability, apoptosis, and cell cycle analyses. Results: Here, we have shown that IR triggers the differential expression of miR-27b in murine thymus tissue in a dose-, time- and sex-dependent manner. miR-27b was significantly down-regulated in leukemia cell lines CCL119 and TIB152. Interestingly, ERα was overexpressed in those 2 cell lines, and it was inversely correlated with miR-27b expression. Therefore, we used TIB152 as a model system to determine the role of ERα in miR-27b expression and the contribution of miR-27b to leukemogenesis. β-Estradiol caused a rapid and transient reduction in miR-27b expression reversed by either ERα-neutralizing antibody or ERK1/2 inhibitor. Ectopic expression of miR-27b remarkably suppressed TIB152 cell proliferation, at least in part, by inducing S-phase arrest. In addition, it attenuated the expression of cyclin A2, although it had no effect on the levels of PCNA, PPARγ, CDK2, p21, p27, p-p53, and cleaved caspase-3. Conclusion: Our data reveal that β-estradiol/ERα signaling may contribute to the down-regulation of miR-27b in acute leukemia cell lines through the ERK1/2 pathway, and that miR-27b may function as a tumor

  9. Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells.

    PubMed

    Shi, Hongbo; Zhang, Guangde; Wang, Jing; Wang, Zhenzhen; Liu, Xiaoxia; Cheng, Liang; Li, Weimin

    2016-01-01

    Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI. PMID:27367417

  10. Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells

    PubMed Central

    Wang, Jing; Wang, Zhenzhen; Liu, Xiaoxia; Cheng, Liang; Li, Weimin

    2016-01-01

    Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA–TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA–TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI. PMID:27367417

  11. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database

    PubMed Central

    Chou, Chih-Hung; Chang, Nai-Wen; Shrestha, Sirjana; Hsu, Sheng-Da; Lin, Yu-Ling; Lee, Wei-Hsiang; Yang, Chi-Dung; Hong, Hsiao-Chin; Wei, Ting-Yen; Tu, Siang-Jyun; Tsai, Tzi-Ren; Ho, Shu-Yi; Jian, Ting-Yan; Wu, Hsin-Yi; Chen, Pin-Rong; Lin, Nai-Chieh; Huang, Hsin-Tzu; Yang, Tzu-Ling; Pai, Chung-Yuan; Tai, Chun-San; Chen, Wen-Liang; Huang, Chia-Yen; Liu, Chun-Chi; Weng, Shun-Long; Liao, Kuang-Wen; Hsu, Wen-Lian; Huang, Hsien-Da

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts. PMID:26590260

  12. Risk miRNA screening of ovarian cancer based on miRNA functional synergistic network

    PubMed Central

    2014-01-01

    Background miRNAs are proved to have causal roles in tumorgenesis involving various types of human cancers, but the mechanism is not clear. We aimed to explore the effect of miRNAs on the development of ovarian cancer and the underlying mechanism. Methods The miRNA expression profile GSE31801 was downloaded from GEO (Gene Expression Omnibus) database. Firstly, the differentially expressed miRNAs were screened. Target genes of the miRNAs were collected from TargetScan, PicTar, miRanda, and DIANA-microT database, then the miRNA-miRNA co-regulating network was constructed using miRNA pairs with common regulated target genes. Next, the functional modules in the network were studied, the miRNA pairs regulated at least one modules were enriched to form the miRNA functional synergistic network (MFSN). Results Risk miRNA were selected in MFSN according to the topological structure. Transcript factors (TFs) in MFSN were identified, followed by the miRNA-transcript factor networks construction. Totally, 42 up- and 61 down-regulated differentially expressed miRNAs were identified, of which 68 formed 2292 miRNA pairs in the miRNA-miRNA co-regulating network. GO: 0007268 (synaptic transmission) and GO: 0019226 (transmission of nerve impulse) were the two common functions of miRNAs in MFSN, and hsa-miR-579 (36), hsa-miR-942 (31), hsa-miR-105 (31), hsa-miR-150 (34), and hsa-miR-27a* (32) were selected as the hub nodes in MFSN. Conclusions In all, 17 TFs, including CREM, ERG, and CREB1 were screened as the cancer related TFs in MFSN. Other TFs, such as BIN1, FOXN3, FOXK1, FOXP2, and ESRRG with high degrees may be inhibited in ovarian cancer. MFSN gave us a new shed light on the mechanism studies in ovarian cancer. PMID:24444095

  13. miR-190b is markedly upregulated in the intestine in response to SIV replication and partly regulates myotubularin related protein-6 expression

    PubMed Central

    Mohan, Mahesh; Chandra, Lawrance C.; Torben, Workineh; Aye, Pyone P.; Alvarez, Xavier; Lackner, Andrew A.

    2014-01-01

    HIV replication and the cellular miRNA machinery interconnect at several post-transcriptional levels. To understand their regulatory role in the intestine, a major site of HIV/SIV replication, dissemination and CD4+ T cell depletion we profiled miRNA expression in colon following SIV infection (10-Acute-SIV, 5-uninfected). Nine (4-up and 5-down) miRNAs showed statistically significant differential expression. Most notably, miR-190b expression showed high statistical significance (Adjusted p=0.0032), the greatest fold change and was markedly elevated in colon and jejunum throughout SIV infection. Additionally, miR-190b upregulation was detected before peak viral replication and the nadir of CD4+ T cell depletion predominantly in lamina propria leukocytes. Interestingly non-SIV-infected macaques with diarrhea and colitis failed to upregulate miR-190b suggesting that its upregulation was neither inflammation nor immune-activation driven. SIV infection of in vitro cultured CD4+ T cells and primary intestinal macrophages conclusively identified miR-190b upregulation to be driven in response to viral replication. Further miR-190b expression levels in colon and jejunum positively correlated with tissue viral loads. In contrast, mRNA expression of MTMR6, a negative regulator of CD4+ T cell activation/proliferation significantly decreased in SIV-infected macrophages. Luciferase reporter assays confirmed MTMR6 as a direct miR-190b target. This first report describing dysregulated miRNA expression in the intestine identifies a potentially significant role for miR-190b in HIV/SIV pathogenesis. More importantly, miR-190b mediated MTMR6 downregulation suggests an important mechanism that could keep infected cells in an activated state thereby promoting viral replication. In future, the mechanisms driving miR-190b upregulation including other cellular processes it regulates in SIV-infected cells needs determination. PMID:24981450

  14. MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells.

    PubMed

    Formosa, A; Markert, E K; Lena, A M; Italiano, D; Finazzi-Agro', E; Levine, A J; Bernardini, S; Garabadgiu, A V; Melino, G; Candi, E

    2014-10-30

    miRNAs act as oncogenes or tumor suppressors in a wide variety of human cancers, including prostate cancer (PCa). We found a severe and consistent downregulation of miRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 region in metastatic cell lines as compared with normal prostatic epithelial cells (PrEC). In specimens of human prostate (28 normals, 99 primary tumors and 13 metastases), lower miRNA levels correlated significantly with a higher incidence of metastatic events and higher prostate specific antigen (PSA) levels, with similar trends observed for lymph node invasion and the Gleason score. We transiently transfected 10 members of the 14q32.31 cluster in normal prostatic epithelial cell lines and characterized their affect on malignant cell behaviors, including proliferation, apoptosis, migration and invasion. Finally, we identified FZD4, a gene important for epithelial-to-mesenchymal transition in (PCa), as a target of miR-377. PMID:24166498

  15. miRClassify: an advanced web server for miRNA family classification and annotation.

    PubMed

    Zou, Quan; Mao, Yaozong; Hu, Lingling; Wu, Yunfeng; Ji, Zhiliang

    2014-02-01

    MicroRNA (miRNA) family is a group of miRNAs that derive from the common ancestor. Normally, members from the same miRNA family have similar physiological functions; however, they are not always conserved in primary sequence or secondary structure. Proper family prediction from primary sequence will be helpful for accurate identification and further functional annotation of novel miRNA. Therefore, we introduced a novel machine learning-based web server, the miRClassify, which can rapidly identify miRNA from the primary sequence and classify it into a miRNA family regardless of similarity in sequence and structure. Additionally, the medical implication of the miRNA family is also provided when it is available in PubMed. The web server is accessible at the link http://datamining.xmu.edu.cn/software/MIR/home.html. PMID:24480175

  16. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease

    PubMed Central

    Elia, Leonardo; Quintavalle, Manuela; Zhang, Jianlin; Contu, Riccardo; Cossu, Luca; Latronico, Michael V. G.; Peterson, Kirk L.; Indolfi, Ciro; Catalucci, Daniele; Chen, Ju; Courtneidge, Sara A.; Condorelli, Gianluigi

    2010-01-01

    Mechanisms controlling vascular smooth muscle cell (VSMC) plasticity and renewal still remain to be completely elucidated. A class of small RNAs called microRNAs (miRs) regulate gene expression at the post-transcriptional level. Here we demonstrate a critical role of the miR-143/145 cluster in SMC differentiation and vascular pathogenesis, also through the generation of a mouse model of miR-143 and -145 knockout. We determined that the expression of miR-143 and -145 is decreased in acute and chronic vascular stress (transverse aortic constriction and in aortas of the ApoE knockout mouse). In human aortic aneurysms, the expression of miR-143 and -145 was significantly decreased compared to control aortas. In addition, overexpression of miR-143 and -145 decreased neointimal formation in a rat model of acute vascular injury. An in-depth analysis of the miR-143/145 knockout mouse model demonstrated that this miR cluster is expressed mostly in the SMC compartment, both during development and post-natally, in vessels and SMC-containing organs. Loss of miR-143 and miR-145 expression induces structural modifications of the aorta, due to an incomplete differentiation of VSMCs. In conclusion, our results demonstrate that the miR-143/145 gene cluster plays a critical role during SMC differentiation and strongly suggest its involvement in the reversion of the VSMC differentiation phenotype that occurs during vascular disease. PMID:19816508

  17. Computational and in vitro Investigation of miRNA-Gene Regulations in Retinoblastoma Pathogenesis: miRNA Mimics Strategy

    PubMed Central

    Venkatesan, Nalini; Deepa, Perinkulam Ravi; Khetan, Vikas; Krishnakumar, Subramanian

    2015-01-01

    PURPOSE Retinoblastoma (RB), a primary pediatric intraocular tumor, arises from primitive retinal layers. Several novel molecular strategies are being developed for the clinical management of RB. miRNAs are known to regulate cancer-relevant biological processes. Here, the role of selected miRNAs, namely, miR-532-5p and miR-486-3p, has been analyzed for potential therapeutic targeting in RB. METHODS A comprehensive bioinformatic analysis was performed to predict the posttranscriptional regulators (miRNAs) of the select panel of genes [Group 1: oncogenes (HMGA2, MYCN, SYK, FASN); Group 2: cancer stem cell markers (TACSTD, ABCG2, CD133, CD44, CD24) and Group 3: cell cycle regulatory proteins (p53, MDM2)] using Microcosm, DIANALAB, miRBase v 18, and REFSEQ database, and RNA hybrid. The expressions of five miRNAs, namely, miR-146b-5p, miR-532-5p, miR-142-5p, miR-328, and miR-486-3p, were analyzed by qRT–PCR on primary RB tumor samples (n = 30; including 17 invasive RB tumors and 13 noninvasive RB tumors). Detailed complementary alignment between 5’ seed sequence of differentially expressed miRNAs and the sequence of target genes was determined. Based on minimum energy level and piCTAR scores, the gene targets were selected. Functional roles of these miRNA clusters were studied by using mimics in cultured RB (Y79, Weri Rb-1) cells in vitro. The gene targets (SYK and FASN) of the studied miRNAs were confirmed by qRT-PCR and western blot analysis. Cell proliferation and apoptotic studies were performed. RESULTS Nearly 1948 miRNAs were identified in the in silico analysis, From this list, only 9 upregulated miRNAs (miR-146b-5p, miR-305, miR-663b, miR-299, miR-532-5p, miR-892b, miR-501, miR-142-5p, and miR-513b) and 10 downregulated miRNAs (miR-1254, miR-328, miR-133a, miR-1287, miR-1299, miR-375, miR-486-3p, miR-720, miR-98, and miR-122*) were found to be common with the RB serum miRNA profile. Downregulation of five miRNAs (miR-146b-5p, miR-532-5p, miR-142-5p, miR-328

  18. Unilateral Breast Reconstruction Using Bilateral Inferior Gluteal Artery Perforator Flaps

    PubMed Central

    Muto, Mayu; Ogawa, Marina; Shibuya, Mai; Yasumura, Kazunori; Kobayashi, Shinji; Ishikawa, Takashi; Maegawa, Jiro

    2015-01-01

    Background: For reconstructing moderate-to-high projection breasts in nulliparous patients with insufficient abdominal tissue or prior abdominal surgeries, a unilateral inferior gluteal artery perforator (IGAP) flap is an alternative procedure. In patients with slim hips, however, unilateral gluteal tissue is insufficient and inferior gluteal crease displacement may develop postoperatively. Donor-site asymmetry is also a major disadvantage. In these circumstances, bilateral IGAP flaps provide sufficient tissue without significant gluteal deformity. Methods: We retrospectively reviewed 20 patients who underwent unilateral breast reconstruction using bilateral IGAP flaps by a single surgeon between November 2007 and December 2012. A quantitative outcome assessment was performed and compared with that of 22 unilateral IGAP flap patients operated on by the same surgeon. Results: Twenty patients underwent reconstruction with 40 IGAP flaps. Of the 40 flaps, 39 survived and 1 developed total necrosis due to repeated venous thrombosis. In 15 of 20 patients, the size of reconstructed breast was comparable to that of the contralateral breast. Final inset flap weight was 462.3 g for bilateral flaps and 244.3 g for unilateral flaps. Total operating time was 671.1 minutes (bilateral flaps) and 486.8 minutes (unilateral flaps). Conclusions: Use of bilateral IGAP flaps for breast reconstruction helps to avoid asymmetry of the inferior buttock volume and shape. Bilateral flaps provide sufficient tissue volume and allow for reconstruction of a breast comparable to the unaffected side. In patients with moderate-to-high projection breast whose abdominal tissue cannot be used for reconstruction, IGAP flaps may be a suitable alternative. PMID:25878925

  19. miRNAs in human cancer

    PubMed Central

    Farazi, Thalia A.; Spitzer, Jessica I.; Morozov, Pavel; Tuschl, Thomas

    2010-01-01

    Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20- to 23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is mostly achieved through specific base-pairing interactions between the 5′ end (“seed” region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers. PMID:21125669

  20. miRNA sensitivity to Drosha levels correlates with pre-miRNA secondary structure

    PubMed Central

    Sperber, Henrik; Beem, Alan; Shannon, Sandra; Jones, Ross; Banik, Pratyusha; Chen, Yu; Ku, Sherman; Varani, Gabriele; Yao, Shuyuan; Ruohola-Baker, Hannele

    2014-01-01

    microRNAs (miRNAs) are crucial for cellular development and homeostasis. In order to better understand regulation of miRNA biosynthesis, we studied cleavage of primary miRNAs by Drosha. While Drosha knockdown triggers an expected decrease of many mature miRNAs in human embryonic stem cells (hESC), a subset of miRNAs are not reduced. Statistical analysis of miRNA secondary structure and fold change of expression in response to Drosha knockdown showed that absence of mismatches in the central region of the hairpin, 5 and 9–12 nt from the Drosha cutting site conferred decreased sensitivity to Drosha knockdown. This suggests that, when limiting, Drosha processes miRNAs without mismatches more efficiently than mismatched miRNAs. This is important because Drosha expression changes over cellular development and the fold change of expression for miRNAs with mismatches in the central region correlates with Drosha levels. To examine the biochemical relationship directly, we overexpressed structural variants of miRNA-145, miRNA-137, miRNA-9, and miRNA-200b in HeLa cells with and without Drosha knockdown; for these miRNAs, elimination of mismatches in the central region increased, and addition of mismatches decreased their expression in an in vitro assay and in cells with low Drosha expression. Change in Drosha expression can be a biologically relevant mechanism by which eukaryotic cells control miRNA profiles. This phenomenon may explain the impact of point mutations outside the seed region of certain miRNAs. PMID:24677349

  1. miRNA polymorphisms (miR‑146a, miR‑149, miR‑196a2 and miR‑499) are associated with the risk of coronary artery disease.

    PubMed

    Sung, Jung-Hoon; Kim, Sang-Hoon; Yang, Woo-In; Kim, Won-Jang; Moon, Jae-Youn; Kim, In Jai; Cha, Dong-Hun; Cho, Seung-Yun; Kim, Jung Oh; Kim, Kyeong Ah; Kim, Ok-Joon; Lim, Sang-Wook; Kim, Nam-Keun

    2016-09-01

    Small non‑coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis‑related diseases. However, the effect of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction‑amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR‑146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR‑146aG/‑149T/‑196a2C/‑499 G allele combination was significantly associated with CAD prevalence (G‑T‑C‑G and G‑C‑C‑G of miR‑146a/‑149/‑196a2/‑499). The combination genotypes of miR‑146aGG/149TC+CC and miR‑149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR‑146a rs2910164 C>G increased the risk of developing CAD in non‑smoking, hypertensive and nondiabetic subgroups. Furthermore, miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR‑149T allele, miR‑196a2C allele and miR‑146aG/‑149T/‑196a2C/‑499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence. PMID:27430349

  2. Inferior Vena Cava Duplication: Incidental Case in a Young Woman

    PubMed Central

    Coco, Danilo; Cecchini, Sara; Leanza, Silvana; Viola, Massimo; Ricci, Stefano; Campagnacci, Roberto

    2016-01-01

    A case of a double inferior vena cava (IVC) with retroaortic left renal vein, azygos continuation of the IVC, and presence of the hepatic portion of the IVC drained into the right renal vein is reported and the embryologic, clinical, and radiological significance is discussed. The diagnosis is suggested by multidetector computed tomography (MDCT), which reveals the aberrant vascular structures. Awareness of different congenital anomalies of IVC is necessary for radiologists to avoid diagnostic pitfalls and they should be remembered because they can influence several surgical interventions and endovascular procedures. PMID:27217964

  3. Inferior Vena Cava Duplication: Incidental Case in a Young Woman.

    PubMed

    Coco, Danilo; Cecchini, Sara; Leanza, Silvana; Viola, Massimo; Ricci, Stefano; Campagnacci, Roberto

    2016-01-01

    A case of a double inferior vena cava (IVC) with retroaortic left renal vein, azygos continuation of the IVC, and presence of the hepatic portion of the IVC drained into the right renal vein is reported and the embryologic, clinical, and radiological significance is discussed. The diagnosis is suggested by multidetector computed tomography (MDCT), which reveals the aberrant vascular structures. Awareness of different congenital anomalies of IVC is necessary for radiologists to avoid diagnostic pitfalls and they should be remembered because they can influence several surgical interventions and endovascular procedures. PMID:27217964

  4. Bruxism elicited by inferior alveolar nerve injury: a case report.

    PubMed

    Melis, Marcello; Coiana, Carlo; Secci, Simona

    2012-02-01

    The aim of this case report is to describe the history of a patient who received an injury to the right inferior alveolar nerve after placement of a dental implant, with bruxism noted afterward. The symptoms were managed by the use of an occlusal appliance worn at night and occasionally during the day, associated with increased awareness of parafunction during the day to reduce muscle pain and fatigue. Paresthesia of the teeth, gingiva, and lower lip persisted but were reduced during appliance use. PMID:22254232

  5. Focal elastic obstruction of the inferior vena cava.

    PubMed

    Helmy, T; Ware, D L; Patterson, C; Stouffer, G A

    2000-12-01

    Obstruction of the supra-hepatic inferior vena cava (IVC) is a common cause of hepatic venous hypertension and the most common cause of Budd-Chiari Syndrome. Because most cases of IVC obstruction go undiagnosed until Budd-Chiari Syndrome develops, the natural history of IVC obstruction is not well defined. We report a case of a focal, elastic, non-membranous obstruction of the IVC causing hepatic venous hypertension and elevated serum transaminases in a 36-year-old man. The obstruction was successfully treated with placement of a self-expanding metallic stent with normalization of hepatic transaminases. PMID:11108690

  6. Hypertrophy of the Inferior Olivary Nucleus Impacts Perception of Gravity

    PubMed Central

    Tarnutzer, Alexander A.; Palla, Antonella; Marti, Sarah; Schuknecht, Bernhard; Straumann, Dominik

    2012-01-01

    Interruption of the dentato-olivary projections, interconnecting the dentate nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted to interfere with the DN’ role in estimating direction of gravity. In a patient with pendular nystagmus due to hypertrophy of the ION secondary to predominantly right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from clockwise to counter-clockwise deviations within 4 months. We hypothesize that synchronized oscillations of ION neurons induce a loss of inhibitory control, leading to hyperactivity of the contralateral DN and, as a result, to perceived vertical roll–tilt to the side of the over-active DN. PMID:22593754

  7. The inferior vena cava clip. The percutaneous approach.

    PubMed

    Bildsoe, M C; Yedlicka, J W; Hunter, D W; Castañeda-Zúñiga, W R; Amplatz, K

    1990-08-01

    Pulmonary embolism in high-risk patients may be minimized by surgical inferior vena cava (IVC) clipping or by the insertion of caval filters. A percutaneous clipping technique was developed that narrows the cava while allowing caval patency. The caval clip is inserted through a percutaneous translumbar approach under fluoroscopic control. Nine dogs underwent percutaneous translumbar caval clip placement without complications. Three of four dogs, followed-up for 5 to 19 weeks by angiography and caval pressure measurements, showed caval patency. This technique eliminates the risks of surgical IVC clip placement and risks from the insertion of intravascular foreign bodies such as filters. PMID:2394568

  8. Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

    PubMed Central

    Lever, Michael; George, Peter M.; Elmslie, Jane L.; Atkinson, Wendy; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

    2012-01-01

    Background Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. Methods Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. Principal Findings The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). Conclusions Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk. PMID:22649561

  9. Non-inhibited miRNAs shape the cellular response to anti-miR

    PubMed Central

    Androsavich, John R.; Chau, B. Nelson

    2014-01-01

    Identification of primary microRNA (miRNA) gene targets is critical for developing miRNA-based therapeutics and understanding their mechanisms of action. However, disentangling primary target derepression induced by miRNA inhibition from secondary effects on the transcriptome remains a technical challenge. Here, we utilized RNA immunoprecipitation (RIP) combined with competitive binding assays to identify novel primary targets of miR-122. These transcripts physically dissociate from AGO2-miRNA complexes when anti-miR is spiked into liver lysates. mRNA target displacement strongly correlated with expression changes in these genes following in vivo anti-miR dosing, suggesting that derepression of these targets directly reflects changes in AGO2 target occupancy. Importantly, using a metric based on weighted miRNA expression, we found that the most responsive mRNA target candidates in both RIP competition assays and expression profiling experiments were those with fewer alternative seed sites for highly expressed non-inhibited miRNAs. These data strongly suggest that miRNA co-regulation modulates the transcriptomic response to anti-miR. We demonstrate the practical utility of this ‘miR-target impact’ model, and encourage its incorporation, together with the RIP competition assay, into existing target prediction and validation pipelines. PMID:24810853

  10. miRTex: A Text Mining System for miRNA-Gene Relation Extraction

    PubMed Central

    Li, Gang; Ross, Karen E.; Arighi, Cecilia N.; Peng, Yifan; Wu, Cathy H.; Vijay-Shanker, K.

    2015-01-01

    MicroRNAs (miRNAs) regulate a wide range of cellular and developmental processes through gene expression suppression or mRNA degradation. Experimentally validated miRNA gene targets are often reported in the literature. In this paper, we describe miRTex, a text mining system that extracts miRNA-target relations, as well as miRNA-gene and gene-miRNA regulation relations. The system achieves good precision and recall when evaluated on a literature corpus of 150 abstracts with F-scores close to 0.90 on the three different types of relations. We conducted full-scale text mining using miRTex to process all the Medline abstracts and all the full-length articles in the PubMed Central Open Access Subset. The results for all the Medline abstracts are stored in a database for interactive query and file download via the website at http://proteininformationresource.org/mirtex. Using miRTex, we identified genes potentially regulated by miRNAs in Triple Negative Breast Cancer, as well as miRNA-gene relations that, in conjunction with kinase-substrate relations, regulate the response to abiotic stress in Arabidopsis thaliana. These two use cases demonstrate the usefulness of miRTex text mining in the analysis of miRNA-regulated biological processes. PMID:26407127

  11. Evaluation of inhibition of miRNA expression induced by anti-miRNA oligonucleotides.

    PubMed

    Chae, Dong-Kyu; Ban, Eunmi; Yoo, Young Sook; Baik, Ja-Hyun; Song, Eun Joo

    2016-07-01

    MicroRNAs (miRNAs) are short RNA molecules that control the expression of mRNAs associated with various biological processes. Therefore, deregulated miRNAs play an important role in the pathogenesis of diseases. Numerous studies aimed at developing novel miRNA-based drugs or determining miRNA functions have been conducted by inhibiting miRNAs using anti-miRNA oligonucleotides (AMOs), which inhibit the function by hybridizing with miRNA. To increase the binding affinity and specificity to target miRNA, AMOs with various chemical modifications have been developed. Evaluating the potency of these various types of AMOs is an essential step in their development. In this study, we developed a capillary electrophoresis with laser-induced fluorescence (CE-LIF) method to evaluate the potency of AMOs by measuring changes in miRNA levels with fluorescence-labeled ssDNA probes using AMO-miR-23a, which inhibits miR-23a related to lung cancer. In order to eliminate interference by excess AMOs during hybridization of the ssDNA probe with the miR-23a, the concentration of the ssDNA probe was optimized. This newly developed method was used to compare the potency of two different modified AMOs. The data were supported by the results of a luciferase assay. This study demonstrated that CE-LIF analysis could be used to accurately evaluate AMO potency in biological samples. PMID:27178549

  12. NORTH EMBANKMENT IN FOREGROUND, WITH (LR) SUBSTATION (MI98D), POWERHOUSE (MI98C), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    NORTH EMBANKMENT IN FOREGROUND, WITH (L-R) SUBSTATION (MI-98-D), POWERHOUSE (MI-98-C), AND COOKE DAM POND IN BACKGROUND. VIEW TO SOUTH - Cooke Hydroelectric Plant, North Embankment, Cook Dam Road at Au Sable River, Oscoda, Iosco County, MI

  13. Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together

    PubMed Central

    Jayapandian, Magesh; Chapman, Adriane; Tarcea, V. Glenn; Yu, Cong; Elkiss, Aaron; Ianni, Angela; Liu, Bin; Nandi, Arnab; Santos, Carlos; Andrews, Philip; Athey, Brian; States, David; Jagadish, H. V.

    2007-01-01

    Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: . PMID:17130145

  14. Spatiotemporal plasticity of miRNAs functions: The miR-17-92 case.

    PubMed

    Bonaldi, Tiziana; Mihailovich, Marija

    2016-05-01

    The functional effect of a specific miRNA is tightly linked to the transcriptome, thus having the potential to elicit distinct outcomes in different cellular states. Our recent discovery of a dual role of the miR-17-92 cluster, which shifts from oncogene to tumor suppressor during lymphoma progression, exemplifies the spatiotemporal plasticity of miRNAs. PMID:27314099

  15. Transcription factor C/EBP-β induces tumor-suppressor phosphatase PHLPP2 through repression of the miR-17-92 cluster in differentiating AML cells.

    PubMed

    Yan, Y; Hanse, E A; Stedman, K; Benson, J M; Lowman, X H; Subramanian, S; Kelekar, A

    2016-07-01

    PHLPP2, a member of the PH-domain leucine-rich repeat protein phosphatase (PHLPP) family, which targets oncogenic kinases, has been actively investigated as a tumor suppressor in solid tumors. Little is known, however, regarding its regulation in hematological malignancies. We observed that PHLPP2 protein expression, but not its mRNA, was suppressed in late differentiation stage acute myeloid leukemia (AML) subtypes. MicroRNAs (miR or miRNAs) from the miR-17-92 cluster, oncomir-1, were shown to inhibit PHLPP2 expression and these miRNAs were highly expressed in AML cells that lacked PHLPP2 protein. Studies showed that miR-17-92 cluster regulation was, surprisingly, independent of transcription factors c-MYC and E2F in these cells; instead all-trans-retinoic acid (ATRA), a drug used for terminally differentiating AML subtypes, markedly suppressed miR-17-92 expression and increased PHLPP2 protein levels and phosphatase activity. Finally, we demonstrate that the effect of ATRA on miR-17-92 expression is mediated through its target, transcription factor C/EBPβ, which interacts with the intronic promoter of the miR-17-92 gene to inhibit transactivation of the cluster. These studies reveal a novel mechanism for upregulation of the phosphatase activity of PHLPP2 through C/EBPβ-mediated repression of the miR-17-92 cluster in terminally differentiating myeloid cells. PMID:26868909

  16. Hierarchical Encoding of Social Cues in Primate Inferior Temporal Cortex.

    PubMed

    Morin, Elyse L; Hadj-Bouziane, Fadila; Stokes, Mark; Ungerleider, Leslie G; Bell, Andrew H

    2015-09-01

    Faces convey information about identity and emotional state, both of which are important for our social interactions. Models of face processing propose that changeable versus invariant aspects of a face, specifically facial expression/gaze direction versus facial identity, are coded by distinct neural pathways and yet neurophysiological data supporting this separation are incomplete. We recorded activity from neurons along the inferior bank of the superior temporal sulcus (STS), while monkeys viewed images of conspecific faces and non-face control stimuli. Eight monkey identities were used, each presented with 3 different facial expressions (neutral, fear grin, and threat). All facial expressions were displayed with both a direct and averted gaze. In the posterior STS, we found that about one-quarter of face-responsive neurons are sensitive to social cues, the majority of which being sensitive to only one of these cues. In contrast, in anterior STS, not only did the proportion of neurons sensitive to social cues increase, but so too did the proportion of neurons sensitive to conjunctions of identity with either gaze direction or expression. These data support a convergence of signals related to faces as one moves anteriorly along the inferior bank of the STS, which forms a fundamental part of the face-processing network. PMID:24836688

  17. Using inferior vena cava filters to prevent pulmonary embolism

    PubMed Central

    Chung, John; Owen, Richard J.T.

    2008-01-01

    OBJECTIVE To review the evidence for using inferior vena cava (IVC) filters to prevent pulmonary embolism (PE) in high-risk patients. QUALITY OF EVIDENCE Ovid MEDLINE was searched from 1966 to 2006 for all English-language papers on IVC filters. Evidence was graded according to the 3-level classification system. Most evidence found was level II. MAIN MESSAGE Inferior vena cava filters are used to prevent PE in patients with contraindications to, complications of, or failure of anticoagulation therapy and patients with extensive free-floating thrombi or residual thrombi following massive PE. Current evidence indicates that IVC filters are largely effective; breakthrough PE occurs in only 0% to 6.2% of cases. Contraindications to implantation of IVC filters include lack of venous access, caval occlusion, uncorrectable coagulopathy, and sepsis. Complications include misplacement or embolization of the filter, vascular injury or thrombosis, pneumothorax, and air emboli. Recurrent PE, IVC thrombosis, filter migration, filter fracture, or penetration of the caval wall sometimes occur with long-term use. CONCLUSION When used appropriately, IVC filters are a safe and effective method of preventing PE. Using retrievable filters might reduce long-term complications. PMID:18208955

  18. Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages

    PubMed Central

    Carnuta, Mihaela G.; Sanda, Gabriela M.; Stancu, Camelia S.; Popescu, Andreea C.; Popescu, Mihaela R.; Vlad, Adelina; Dimulescu, Doina R.; Simionescu, Maya; Sima, Anca V.

    2016-01-01

    We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. PMID:27519051

  19. Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages.

    PubMed

    Simionescu, Natalia; Niculescu, Loredan S; Carnuta, Mihaela G; Sanda, Gabriela M; Stancu, Camelia S; Popescu, Andreea C; Popescu, Mihaela R; Vlad, Adelina; Dimulescu, Doina R; Simionescu, Maya; Sima, Anca V

    2016-01-01

    We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients' sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. PMID:27519051

  20. Inferior vena cava reconstruction using fresh inferior vena cava allograft following caval resection for leiomyosarcoma: midterm results.

    PubMed

    Guerrero, Marlon A; Cross, Chadrick A; Lin, Peter H; Keane, Thomas E; Lumsden, Alan B

    2007-07-01

    We present a 56-year-old woman affected by a large leiomyosarcoma originating from the suprarenal inferior vena cava (IVC). A computed tomography (CT) scan revealed near obstruction of the IVC and involvement of the right renal vein. The patient underwent successful en bloc resection of the tumor, right kidney, right adrenal gland, and IVC. Caval reconstruction was performed using a non-type specific allograft, followed by left renal vein re-implantation. The patient tolerated the procedure well without any complications. The use of an IVC allograft allowed for continued graft patency, without the need of immunosuppression or long-term anticoagulation. However, local recurrence did occur. PMID:17606132

  1. Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs in the Bloodstream

    PubMed Central

    Guescini, Michele; Canonico, Barbara; Lucertini, Francesco; Maggio, Serena; Annibalini, Giosué; Barbieri, Elena; Luchetti, Francesca; Papa, Stefano; Stocchi, Vilberto

    2015-01-01

    In the past few years, skeletal muscle has emerged as an important secretory organ producing soluble factors, called myokines, that exert either autocrine, paracrine or endocrine effects. Moreover, recent studies have shown that muscle releases microRNAs into the bloodstream in response to physical exercise. These microRNAs affect target cells, such as hormones and cytokines. The mechanisms underlying microRNA secretion are poorly characterized at present. Here, we investigated whether muscle tissue releases extracellular vesicles (EVs), which carry microRNAs in the bloodstream under physiological conditions such as physical exercise. Using density gradient separation of plasma from sedentary and physically fit young men we found EVs positive for TSG101 and alpha-sarcoglycan (SGCA), and enriched for miR-206. Cytometric analysis showed that the SGCA+ EVs account for 1–5% of the total and that 60–65% of these EVs were also positive for the exosomal marker CD81. Furthermore, the SGCA-immuno captured sub-population of EVs exhibited higher levels of the miR-206/miR16 ratio compared to total plasma EVs. Finally, a significant positive correlation was found between the aerobic fitness and muscle-specific miRNAs and EV miR-133b and -181a-5p were significantly up-regulated after acute exercise. Thus, our study proposes EVs as a novel means of muscle communication potentially involved in muscle remodeling and homeostasis. PMID:25955720

  2. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  3. Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements

    NASA Astrophysics Data System (ADS)

    Richter, C.-P.; Rajguru, S. M.; Matic, A. I.; Moreno, E. L.; Fishman, A. J.; Robinson, A. M.; Suh, E.; Walsh, J. T., Jr.

    2011-10-01

    Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

  4. Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia.

    PubMed

    Swellam, Menha; El-Khazragy, Nashwa

    2016-08-01

    Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers. PMID:26857279

  5. miR-isomiRExp: a web-server for the analysis of expression of miRNA at the miRNA/isomiR levels

    PubMed Central

    Guo, Li; Yu, Jiafeng; Liang, Tingming; Zou, Quan

    2016-01-01

    MicroRNA (miRNA) locus has been found that can generate a series of varied isomiR sequences. Most studies always focus on determining miRNA level, however, the canonical miRNA sequence is only a specific member in the multiple isomiRs. Some studies have shown that isomiR sequences play versatile roles in biological progress, and the analysis and research should be simultaneously performed at the miRNA/isomiR levels. Based on the biological characteristics of miRNA and isomiR, we developed miR-isomiRExp to analyze expression pattern of miRNA at the miRNA/isomiR levels, provide insights into tracking miRNA/isomiR maturation and processing mechanisms, and reveal functional characteristics of miRNA/isomiR. Simultaneously, we also performed expression analysis of specific human diseases using public small RNA sequencing datasets based on the analysis platform, which may help in surveying the potential deregulated miRNA/isomiR expression profiles, especially sequence and function-related isomiRs for further interaction analysis and study. The miR-isomiRExp platform provides miRNA/isomiR expression patterns and more information to study deregulated miRNA loci and detailed isomiR sequences. This comprehensive analysis will enrich experimental miRNA studies. miR-isomiRExp is available at http://mirisomirexp.aliapp.com. PMID:27009551

  6. miR-isomiRExp: a web-server for the analysis of expression of miRNA at the miRNA/isomiR levels.

    PubMed

    Guo, Li; Yu, Jiafeng; Liang, Tingming; Zou, Quan

    2016-01-01

    MicroRNA (miRNA) locus has been found that can generate a series of varied isomiR sequences. Most studies always focus on determining miRNA level, however, the canonical miRNA sequence is only a specific member in the multiple isomiRs. Some studies have shown that isomiR sequences play versatile roles in biological progress, and the analysis and research should be simultaneously performed at the miRNA/isomiR levels. Based on the biological characteristics of miRNA and isomiR, we developed miR-isomiRExp to analyze expression pattern of miRNA at the miRNA/isomiR levels, provide insights into tracking miRNA/isomiR maturation and processing mechanisms, and reveal functional characteristics of miRNA/isomiR. Simultaneously, we also performed expression analysis of specific human diseases using public small RNA sequencing datasets based on the analysis platform, which may help in surveying the potential deregulated miRNA/isomiR expression profiles, especially sequence and function-related isomiRs for further interaction analysis and study. The miR-isomiRExp platform provides miRNA/isomiR expression patterns and more information to study deregulated miRNA loci and detailed isomiR sequences. This comprehensive analysis will enrich experimental miRNA studies. miR-isomiRExp is available at http://mirisomirexp.aliapp.com. PMID:27009551

  7. miRISC recruits decapping factors to miRNA targets to enhance their degradation

    PubMed Central

    Nishihara, Tadashi; Zekri, Latifa; Braun, Joerg E.; Izaurralde, Elisa

    2013-01-01

    MicroRNA (miRNA)-induced silencing complexes (miRISCs) repress translation and promote degradation of miRNA targets. Target degradation occurs through the 5′-to-3′ messenger RNA (mRNA) decay pathway, wherein, after shortening of the mRNA poly(A) tail, the removal of the 5′ cap structure by decapping triggers irreversible decay of the mRNA body. Here, we demonstrate that miRISC enhances the association of the decapping activators DCP1, Me31B and HPat with deadenylated miRNA targets that accumulate when decapping is blocked. DCP1 and Me31B recruitment by miRISC occurs before the completion of deadenylation. Remarkably, miRISC recruits DCP1, Me31B and HPat to engineered miRNA targets transcribed by RNA polymerase III, which lack a cap structure, a protein-coding region and a poly(A) tail. Furthermore, miRISC can trigger decapping and the subsequent degradation of mRNA targets independently of ongoing deadenylation. Thus, miRISC increases the local concentration of the decapping machinery on miRNA targets to facilitate decapping and irreversibly shut down their translation. PMID:23863838

  8. miRNAFold: a web server for fast miRNA precursor prediction in genomes.

    PubMed

    Tav, Christophe; Tempel, Sébastien; Poligny, Laurent; Tahi, Fariza

    2016-07-01

    Computational methods are required for prediction of non-coding RNAs (ncRNAs), which are involved in many biological processes, especially at post-transcriptional level. Among these ncRNAs, miRNAs have been largely studied and biologists need efficient and fast tools for their identification. In particular, ab initio methods are usually required when predicting novel miRNAs. Here we present a web server dedicated for miRNA precursors identification at a large scale in genomes. It is based on an algorithm called miRNAFold that allows predicting miRNA hairpin structures quickly with high sensitivity. miRNAFold is implemented as a web server with an intuitive and user-friendly interface, as well as a standalone version. The web server is freely available at: http://EvryRNA.ibisc.univ-evry.fr/miRNAFold. PMID:27242364

  9. miRNAFold: a web server for fast miRNA precursor prediction in genomes

    PubMed Central

    Tav, Christophe; Tempel, Sébastien; Poligny, Laurent; Tahi, Fariza

    2016-01-01

    Computational methods are required for prediction of non-coding RNAs (ncRNAs), which are involved in many biological processes, especially at post-transcriptional level. Among these ncRNAs, miRNAs have been largely studied and biologists need efficient and fast tools for their identification. In particular, ab initio methods are usually required when predicting novel miRNAs. Here we present a web server dedicated for miRNA precursors identification at a large scale in genomes. It is based on an algorithm called miRNAFold that allows predicting miRNA hairpin structures quickly with high sensitivity. miRNAFold is implemented as a web server with an intuitive and user-friendly interface, as well as a standalone version. The web server is freely available at: http://EvryRNA.ibisc.univ-evry.fr/miRNAFold. PMID:27242364

  10. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  11. Aneurysm in the anterior inferior cerebellar artery-posterior inferior cerebellar artery variant: Case report and review of literature

    PubMed Central

    Akhtar, Saad; Azeem, Abdul; Jiwani, Amyna; Javed, Gohar

    2016-01-01

    Introduction There are variations in the anatomy of the vertebrobasilar system amongst which the Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery (AICA-PICA) variant is thought to have a prevalence of 20–24% (based on retrospective studies). Despite this, aneurysms of the AICA-PICA variant are rare. We present a case of an AICA-PICA aneurysm and discuss its presentation and management, along with a review of literature. Presentation of case We describe the case of a 35 year old female who presented with signs of meningismus. On the basis of radiological imaging it was initially misdiagnosed as a thrombosed arteriovenous malformation (AVM). The patient was eventually discharged with a plan of interval imaging and interventional radiology (if required). The patient presented again with similar signs and symptoms. Re-evaluation of imaging revealed an aneurysm of the AICA-PICA variant which was managed surgically. Discussion Aneurysms of the AICA-PICA variant are rare. The radiological features and surgical management represent a unique clinical entity and are discussed below. Conclusion The prevalence of the AICA-PICA variant might be high but aneurysms in this vessel are rare. The scant knowledge available on this subject makes it a diagnostic difficulty. PMID:27017276

  12. Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval Exercise and Vigorous-Intensity Continuous Exercise

    PubMed Central

    Cui, Shu F.; Wang, Cheng; Yin, Xin; Tian, Dong; Lu, Qiu J.; Zhang, Chen Y.; Chen, Xi; Ma, Ji Z.

    2016-01-01

    High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used

  13. Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval Exercise and Vigorous-Intensity Continuous Exercise.

    PubMed

    Cui, Shu F; Wang, Cheng; Yin, Xin; Tian, Dong; Lu, Qiu J; Zhang, Chen Y; Chen, Xi; Ma, Ji Z

    2016-01-01

    High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used

  14. Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina

    PubMed Central

    McAdams, Ryan M.; Bierle, Craig J.; Boldenow, Erica; Weed, Samantha; Tsai, Jesse; Beyer, Richard P.; MacDonald, James W.; Bammler, Theo K.; Liggitt, H. Denny; Farin, Federico M.; Vanderhoeven, Jeroen

    2015-01-01

    The mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs (miRNAs) are small noncoding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. Using a nonhuman primate model of choriodecidual infection, we sought to determine if differentially expressed miRNAs were associated with acute fetal lung injury. After inoculating 10 chronically catheterized pregnant monkeys (Macaca nemestrina) with either group B streptococcus (GBS) at 1 × 106 CFU (n = 5) or saline (n = 5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled the changes in expression by microarray analysis. We identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of these, only miR-155-5p was validated by quantitative reverse transcription-PCR (P = 0.02). Significantly elevated miR-155-5p expression was also observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]). Overexpression of miR-155-5p in FeAE cells in turn increased the production of IL-6 and CXCL10/gamma interferon-induced protein 10, which are implicated in leukocyte recruitment but also in protection from lung injury. Interestingly, while miR-155-5p decreased fibroblast growth factor 9 (FGF9) expression in a luciferase reporter assay, FGF9 levels were actually increased in GBS-exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal lung development. Thus, upregulation of miR-155-5p may serve as a compensatory mechanism to lessen the increase in FGF9 and prevent aberrant lung development. Understanding the complicated networks regulating lung development in the setting of infection is a key step in identifying how to prevent fetal lung injury leading to bronchopulmonary dysplasia. PMID:26195546

  15. A New Technique for Inferior Hypogastric Plexus Block: A Coccygeal Transverse Approach -A Case Report-

    PubMed Central

    Choi, Hong Seok; Kim, Young Hoon; Han, Jung Woo

    2012-01-01

    Chronic pelvic pain is a common problem with variable etiology. The sympathetic nervous system plays an important role in the transmission of visceral pain regardless of its etiology. Sympathetic nerve block is effective and safe for treatment of pelvic visceral pain. One of them, the inferior hypogastric plexus, is not easily assessable to blockade by local anesthetics and neurolytic agents. Inferior hypogastric plexus block is not commonly used in chronic pelvic pain patients due to pre-sacral location. Therefore, inferior hypogastric plexus is not readily blocked using paravertebral or transdiscal approaches. There is only one report of inferior hypogastric plexus block via transsacral approach. This approach has several disadvantages. In this case a favorable outcome was obtained by using coccygeal transverse approach of inferior hypogastric plexus. Thus, we report a patient who was successfully given inferior hypogastric plexus block via coccygeal transverse approach to treat chronic pelvic pain conditions involving the lower pelvic viscera. PMID:22259715

  16. Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia.

    PubMed

    Sanghvi, Viraj R; Mavrakis, Konstantinos J; Van der Meulen, Joni; Boice, Michael; Wolfe, Andrew L; Carty, Mark; Mohan, Prathibha; Rondou, Pieter; Socci, Nicholas D; Benoit, Yves; Taghon, Tom; Van Vlierberghe, Pieter; Leslie, Christina S; Speleman, Frank; Wendel, Hans-Guido

    2014-11-18

    The posttranscriptional control of gene expression by microRNAs (miRNAs) is highly redundant, and compensatory effects limit the consequences of the inactivation of individual miRNAs. This implies that only a few miRNAs can function as effective tumor suppressors. It is also the basis of our strategy to define functionally relevant miRNA target genes that are not under redundant control by other miRNAs. We identified a functionally interconnected group of miRNAs that exhibited a reduced abundance in leukemia cells from patients with T cell acute lymphoblastic leukemia (T-ALL). To pinpoint relevant target genes, we applied a machine learning approach to eliminate genes that were subject to redundant miRNA-mediated control and to identify those genes that were exclusively targeted by tumor-suppressive miRNAs. This strategy revealed the convergence of a small group of tumor suppressor miRNAs on the Myb oncogene, as well as their effects on HBP1, which encodes a transcription factor. The expression of both genes was increased in T-ALL patient samples, and each gene promoted the progression of T-ALL in mice. Hence, our systematic analysis of tumor suppressor miRNA action identified a widespread mechanism of oncogene activation in T-ALL. PMID:25406379

  17. Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia.

    PubMed

    López-López, Elixabet; Gutiérrez-Camino, Ángela; Piñán, Maria Ángeles; Sánchez-Toledo, José; Uriz, Jose Javier; Ballesteros, Javier; García-Miguel, Purificación; Navajas, Aurora; García-Orad, África

    2014-01-01

    Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL. PMID:24614921

  18. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  19. Indications, Management, and Complications of Temporary Inferior Vena Cava Filters

    SciTech Connect

    Linsenmaier, Ulrich; Rieger, Johannes; Schenk, Franz; Rock, Clemens; Mangel, Eugen; Pfeifer, Klaus Juergen

    1998-11-15

    Purpose: We describe the results of a preliminary prospective study using different recently developed temporary and retrievable inferior vena cava (IVC) filters. Methods: Fifty temporary IVC filters (Guenther, Guenther Tulip, Antheor) were inserted in 47 patients when the required period of protection against pulmonary embolism (PE) was estimated to be less than 2 weeks. The indications were documented deep vein thrombosis (DVT) and temporary contraindications for anticoagulation, a high risk for PE, and PE despite DVT prophylaxis. Results: Filters were removed 1-12 days after placement and nine (18%) had captured thrombi. Complications were one PE during and after removal of a filter, two minor filter migrations, and one IVC thrombosis. Conclusion: Temporary filters are effective in trapping clots and protecting against PE, and the complication rate does not exceed that of permanent filters. They are an alternative when protection from PE is required temporarily, and should be considered in patients with a normal life expectancy.

  20. Subcortical input heterogeneity in the mouse inferior colliculus

    PubMed Central

    Geis, H-Rüdiger A P; van der Heijden, Marcel; Borst, J Gerard G

    2011-01-01

    Abstract Simultaneous intracellular recordings of nearby neocortical neurons have demonstrated that their membrane potentials are highly correlated. The correlation between the spiking activity of nearby neocortical neurons may be much smaller, suggesting that inputs are more similar than outputs. Much less is known about the similarity of inputs in subcortical sensory areas. Here we investigate this question by making simultaneous whole-cell recordings from neighbouring neurons in the dorsal cortex of the mouse inferior colliculus. No evidence for monosynaptic connections between neighbouring cells was observed, suggesting that integration of afferent signals plays a more important role than local processing. The correlation between frequency response areas of neighbouring cells varied but, surprisingly, neighbouring cells were on average not more similar in their responses to tones than non-neighbouring neurons. This large micro-heterogeneity suggests a sparse representation of acoustic features within the dorsal cortex. PMID:21727222

  1. Inferior Vena Cava Filter Erosion Causing Symptomatic Obstructive Hydronephrosis

    PubMed Central

    Locke, Nathan; Duchene, David

    2016-01-01

    Abstract Background: Transcaval inferior vena cava (IVC) filter penetration involving the urinary tract is rare, but has been previously reported. We herein present unique management of symptomatic hydronephrosis secondary to erosion of an IVC filter limb into the lumen of the proximal right ureter. Case Presentation: A 59-year-old woman presented with abdominal and right flank pain in October 2015 and was found to have right hydronephrosis, apparently secondary to obstruction from erosion of an IVC filter limb into the proximal right ureter. This was effectively managed with percutaneous, endovascular, and endourologic procedures, without the need for a major invasive surgical procedure. Conclusion: Endovascular removal of the IVC filter was performed safely in this case and can be considered when the urinary tract is involved in filter erosion.

  2. Providing Context: Medical Device Litigation and Inferior Vena Cava Filters.

    PubMed

    Keller, Eric J; Vogelzang, Robert L

    2016-06-01

    Over the last few years, an increasing number of lawsuits have been filed involving inferior vena cava filters. This has prompted the U.S. Judicial Panel on Multidistrict Litigation to centralize these lawsuits into two multidistrict litigations: one for Cook's filters and one for Bard's. Both sets of cases share similar questions of facts, in particular whether these filters' design and manufacturing practices made them unreasonably prone to serious complications. The resolution of these cases will add to a larger legal debate concerning how much legal protection the 1976 Medical Device Amendments should offer firms from tort liability. As a specialty that often relies on medical devices, it is not only important for interventional radiologists to have a general understanding of medical device litigation but also to reflect upon the approaches to informed consent regarding these devices. PMID:27247482

  3. Posttransplant Complex Inferior Venacava Balloon Dilatation After Hepatic Vein Stenting

    SciTech Connect

    Kohli, Vikas; Wadhawan, Manav; Gupta, Subhash; Roy, Vipul

    2010-02-15

    Orthotopic and living related liver transplantation is an established mode of treatment of end-stage liver disease. One of the major causes of postoperative complications is vascular anastomotic stenosis. One such set of such complications relates to hepatic vein, inferior vena cava (IVC), or portal vein stenosis, with a reported incidence of 1-3%. The incidence of vascular complications is reported to be higher in living donor versus cadaveric liver transplants. We encountered a patient with hepatic venous outflow tract obstruction, where the hepatic vein had been previously stented, but the patient continued to have symptoms due to additional IVC obstruction. The patient required double-balloon dilatation of the IVC simultaneously from the internal jugular vein and IVC.

  4. Acute myocardial infarction following scorpion sting in a case with obstructive coronary artery disease.

    PubMed

    Patra, Soumya; Satish, K; Singla, Vivek; Ravindranath, K S

    2013-01-01

    The occurrence of an acute myocardial infarction (MI) following a scorpion sting has been very rarely reported in the previous literature. Possible pathogenetic mechanisms include severe hypotension due to hypovolaemic shock and coronary spasm with subsequent thrombosis of coronary vessels developed after the release of vasoactive, inflammatory and thrombogenic substances contained in the scorpion venom. All of the previously reported cases had normal coronary angiogram. We report a case of a 65-year-old woman who presented with severe scorpion sting and was treated with prazosin. But a few hours later, she developed acute anterior wall MI. Coronary angiogram revealed the presence of significant stenosis in coronary arteries. As acute MI owing to significant coronary artery disease can be evident after severe scorpion envenomation, so every case of acute coronary syndrome following scorpion sting needs early diagnosis, thorough cardiovascular evaluation and appropriate treatment. PMID:23715842

  5. miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1

    PubMed Central

    Zhang, Yi; Zhou, Shu-yan; Yan, Hai-zhao; Xu, Dan-dan; Chen, Hai-xuan; Wang, Xiao-yan; Wang, Xiao; Liu, Yu-ting; Zhang, Li; Wang, Sheng; Zhou, Peng-jun; Fu, Wu-yu; Ruan, Bi-bo; Ma, Dong-lei; Wang, Ying; Liu, Qiu-ying; Ren, Zhe; Liu, Zhong; Zhang, Rong; Wang, Yi-fei

    2016-01-01

    Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chemo-resistance in multiple cancers. We found that miR-203 expression was down-regulated in CD34 + AML cells as compared with CD34− cells isolated from patients as well as in LSC-enriched (CD34 + CD38−) cell lines KG-1a or MOLM13. Additionally, re-expression of miR-203 led to decreased cell proliferation, self-renewal, and sphere formation in LSCs. Moreover, miR-203 was found to directly target the 3′un-translated regions of survivin and Bmi-1 mRNAs affecting proliferation and self-renewal in LSCs. In this study, we identified a novel miR-203/survivin/Bmi-1 axis involved in the regulation of biological properties of LSCs. This axis may represent a new therapeutic target for acute myeloid leukemia and a potential prognosis/diagnostic marker for LSCs therapy. PMID:26847520

  6. Expression Change of miR-214 and miR-135 during Muscle Differentiation

    PubMed Central

    Honardoost, Maryam; Soleimani, Masoud; Arefian, Ehsan; Sarookhani, Mohammad reza

    2015-01-01

    Objective MicroRNAs (miRNAs) are a class of small non-coding RNAs that play pivotal roles in many biological processes such as regulating skeletal muscle development where alterations in miRNA expression are reported during myogenesis. In this study, we aimed to investigate the impact of predicted miRNAs and their target genes on the myoblast to myocyte differentiation process. Materials and Methods This experimental study was conducted on the C2C12 cell line. Using a bioinformatics approach, miR-214 and miR-135 were selected according to their targets as potential factors in myoblast to myocyte differentiation induced by 3% horse serum. Immunocytochemistry (ICC) was undertaken to confirm the differentiation process and quantitative real-time polymerase chain reaction (PCR) to determine the expression level of miRNAs and their targets. Results During myoblast to myocyte differentiation, miR-214 was significantly down- regulated while miRNA-135, Irs2, Akt2 and Insr were overexpressed during the process. Conclusion miR-214 and miR-135 are potential regulators of myogenesis and are involved in skeletal muscle development through regulating the IRS/PI3K pathway. PMID:26464817

  7. miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

    PubMed Central

    Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark; Berry, Emily; Morton, Sarah U.; Muth, Alecia N.; Lee, Ting-Hein; Miano, Joseph M.; Ivey, Kathryn N.; Srivastava, Deepak

    2009-01-01

    SUMMARY microRNAs are regulators of myriad cellular events, but evidence for a single microRNA that can efficiently differentiate multipotent cells into a specific lineage or regulate direct reprogramming of cells into an alternate cell fate has been elusive. Here, we show that miR-145 and miR-143 are co-transcribed in multipotent cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem cell–derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2.5, and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4, myocardin, and Elk-1 to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells. PMID:19578358

  8. Serum miR-206 and miR-132 as Potential Circulating Biomarkers for Mild Cognitive Impairment.

    PubMed

    Xie, Bing; Zhou, Huimin; Zhang, Rui; Song, Mei; Yu, Lulu; Wang, Lan; Liu, Zanchao; Zhang, Qingfu; Cui, Dongsheng; Wang, Xueyi; Xu, Shunjiang

    2015-01-01

    MicroRNAs (miRNAs), a class of small, non-coding RNA molecules with gene regulatory functions, have emerged to play a critical role in the pathogenesis of a variety of diseases. Recently, circulating miRNAs have been reported as potential biomarkers for various pathologic conditions. The present study was performed to investigate the potential role of circulating miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI). We collected 66 patients with MCI and 76 normal controls from our previous cross-sectional cohort study. Seven miRNAs (miR-206, miR-132, miR-193b, miR-130b, miR-20a, miR-296, and miR-329) related to Alzheimer's disease (AD) were detected in serum using a quantitative real-time PCR (qRT-PCR) method. Each miRNA's diagnostic performance was evaluated by receiver operating characteristic curves and the areas under curves (AUC) analysis. The levels of miR-206 and miR-132 in MCI patients' serum were significantly elevated compared to normal controls. Combining detection of miR-206 and miR-132 achieved the highest AUC of 0.981, followed by test of miR-206 (AUC = 0.880) and miR-132 (AUC = 0.912) separately. Importantly, miR-206 and miR-132 were respectively correlated with the Montreal Cognitive Assessment score in MCI patients. These results preliminarily indicated that circulating miR-206 and miR-132 as novel miRNAs upregulated in MCI patient were potential biomarkers for diagnosis of MCI. PMID:25589731

  9. MiR-221 and miR-130a Regulate Lung Airway and Vascular Development

    PubMed Central

    Mujahid, Sana

    2013-01-01

    Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin) immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U) were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung. PMID:23409087

  10. Up-regulation of miR-21 and miR-23a Contributes to As2 O3 -induced hERG Channel Deficiency.

    PubMed

    Zhao, Xin; Shi, Yuan-Qi; Yan, Cai-Chuan; Feng, Pan-feng; Wang, Xue; Zhang, Rui; Zhang, Xiao; Li, Bao-Xin

    2015-06-01

    Arsenic trioxide (As2O3) is used to treat acute pro-myelocytic leukaemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As2O3 can damage the hERG current via disturbing its trafficking to cellular membrane. Consistent with these findings, in this study, we reported that As2O3 inhibited hERG channel at both protein and mRNA levels and damaged hERG current but did not affect channel kinetics. Further, we demonstrated that As2O3 up-regulated miR-21 and miR-23a expression in hERG-HEK293 cells and neonatal cardiomyocytes. In addition, knock-down of miR-21 by its specific antisense molecules AMO-21 was able to rescue Sp1 and hERG inhibition caused by As2O3. Consistently, phosphorylation of NF-κB, the upstream regulatory factor of miR-21, was significantly up-regulated by As2O3 . This finding revealed that regulation of the NF-κB-miR-21-Sp1 signalling pathway is a novel mechanism for As2O3-induced hERG inhibition. Meanwhile, the expression of Hsp90 and hERG was rescued by transfection with AMO-23a. And the hERG channel inhibition induced by As2O3 was rescued after being transfected with AMO-23a, which may be a molecular mechanism for the role of As2O3 in hERG trafficking deficiency. In brief, our study revealed that miR-21 and miR-23a are involved in As2O3-induced hERG deficiency at transcriptional and transportational levels. This discovery may provide a novel mechanism of As2O3-induced hERG channel deficiency, and these miRNAs may serve as potential therapeutic targets for the handling of As2O3 cardiotoxicity. PMID:25395240

  11. Genome-Wide Analysis of Small RNA and Novel MicroRNA Discovery in Human Acute Lymphoblastic Leukemia Based on Extensive Sequencing Approach

    PubMed Central

    Zhang, Peng; Chen, Xiao; Wu, Jun; Xu, Ling; Luo, Xue-Qun; Ke, Zhi-Yong; Zhou, Hui; Qu, Liang-Hu; Chen, Yue-Qin

    2009-01-01

    Background MicroRNAs (miRNAs) have been proved to play an important role in various cellular processes and function as tumor suppressors or oncogenes in cancers including leukemia. The identification of a large number of novel miRNAs and other small regulatory RNAs will provide valuable insights into the roles they play in tumorgenesis. Methodology/Principal Findings To gain further understanding of the role of miRNAs relevant to acute lymphoblastic leukemia (ALL), we employed the sequencing-by-synthesis (SBS) strategy to sequence small RNA libraries prepared from ALL patients and normal donors. In total we identified 159 novel miRNAs and 116 novel miRNA*s from both libraries. Among the 159 novel miRNAs, 42 were identified with high stringency in our data set. Furthermore, we demonstrated the different expression patterns of 20 newly identified and several known miRNAs between ALL patients and normal donors, suggesting these miRNAs may be associated with ALL and could constitute an ALL-specific miRNA signature. Interestingly, GO “biological process” classifications revealed that a set of significantly abnormally expressed miRNAs are associated with disease relapse, which implies that these dysregulated miRNAs might promote the progression of ALL by regulating genes involved in the pathway of the disease development. Conclusion/Significance The study presents a comprehensive picture of the expression of small RNAs in human acute lymphoblastic leukemia and highlights novel and known miRNAs differentially expressed between ALL patients and normal donors. To our knowledge, this is the first study to look at genome-wide known and novel miRNA expression patterns in in human acute lymphoblastic leukemia. Our data revealed that these deregulated miRNAs may be associated with ALL or the onset of relapse. PMID:19724645

  12. Circulating extracellular miR-22, miR-155, and miR-365 as candidate biomarkers to assess transport-related stress in turkeys.

    PubMed

    Lecchi, C; Marques, A T; Redegalli, M; Meani, S; Vinco, L J; Bronzo, V; Ceciliani, F

    2016-07-01

    MicroRNA (miRNA) have been identified in circulating blood and might have the potential to be used as biomarkers for several pathophysiological conditions. To identify miRNA that are altered following stress events, turkeys (Meleagris gallopavo) were subjected to 2 h of road transportation. The expression levels of five circulating miRNA, namely miR-22, miR-155-5p, miR-181a-3p, miR-204 and miR-365-3p, were detected and assessed by quantitative polymerase chain reaction using TaqMan® probes, as potential biomarkers of stress. The areas under the receiver operating characteristic curves were then used to evaluate the diagnostic performance of miRNA. A panel of three stress-responsive miRNA, miR-22, miR-155 and miR-365 were identified; their expression levels were significantly higher after road transportation and the area under the curve (AUC) were 0.763, 0.71 and 0.704, respectively. Combining the three miRNA a specificity similar to the one found for the three miRNA separately was found. The AUC of the weighted average of the three miRNA was 0.763. This preliminary study suggests that the expression levels of circulating miR-22, miR-155 and miR-365 are increased during transport-related stress and that they may have diagnostic value to discriminate between stressed- and unstressed animals. PMID:26760121

  13. Clinical significance of microRNAs in chronic and acute human leukemia.

    PubMed

    Yeh, Chien-Hung; Moles, Ramona; Nicot, Christophe

    2016-01-01

    Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID:27179712

  14. Influence of interstitial Mn on magnetism in the room-temperature ferromagnet <mi>Mn>1+<mi>δSb>

    SciTech Connect

    Taylor, Alice E.; Berlijn, Tom; Hahn, Steven E.; May, Andrew F.; Williams, Travis J.; Poudel, Lekhanath N; Calder, Stuart A.; Fishman, Randy Scott; Stone, Matthew B.; Aczel, Adam A.; Cao, Huibo; Lumsden, Mark D.; Christianson, Andrew D.

    2015-06-15

    We report elastic and inelastic neutron scattering measurements of the high-TC ferromagnet <mi>Mn>1+<mi>δSb>. Measurements were performed on a large, TC = 434 K, single crystal with interstitial Mn content of δ ≈ 0.13. The neutron diffraction results reveal that the interstitial Mn has a magnetic moment, and that it is aligned antiparallel to the main Mn moment. We perform density functional theory calculations including the interstitial Mn, and find the interstitial to be magnetic in agreement with the diffraction data. The inelastic neutron scattering measurements reveal two features in the magnetic dynamics: i) a spin-wave-like dispersion emanating from ferromagnetic Bragg positions (H K 2n), and ii) a broad, non-dispersive signal centered at forbidden Bragg positions (H K 2n+1). The inelastic spectrum cannot be modeled by simple linear spin-wave theory calculations, and appears to be significantly altered by the presence of the interstitial Mn ions. Finally, the results show that the influence of the interstitial Mn on the magnetic state in this system is more important than previously understood.

  15. MI high power operation and future plans

    SciTech Connect

    Kourbanis, Ioanis; /Fermilab

    2008-09-01

    Fermilab's Main Injector on acceleration cycles to 120 GeV has been running a mixed mode operation delivering beam to both the antiproton source for pbar production and to the NuMI[1] target for neutrino production since 2005. On January 2008 the slip stacking process used to increase the beam to the pbar target was expanded to include the beam to the NuMI target increasing both the beam intensity and power. The current high power MI operation will be described along with the near future plans.

  16. miR-200a/miR-141 and miR-205 upregulation might be associated with hormone receptor status and prognosis in endometrial carcinomas

    PubMed Central

    Dong, Ying; Si, Jing-Wen; Li, Wen-Ting; Liang, Li; Zhao, Jian; Zhou, Mei; Li, Dong; Li, Ting

    2015-01-01

    The aim of this study was to compare the clinicopathological significance of miR-200a/miR-141 and miR-205 expression in endometrioid carcinomas (ECs) versus nonendometrioid carcinomas (NECs) and to assess their correlation with hormone receptor status. miR-200a/miR-141 and miR-205 expression in 154 endometrial cancers was determined by qRT-PCR. The status of estrogen and progesterone receptor (ER/PR) was assessed using immunohistochemistry. miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. The expression level of miR-200a was significantly higher in NECs than in ECs (P = 0.025). Furthermore, there was a trend that NECs with worse clinicopathological variables had a higher miR-200a expression, while an inverse trend existed in ECs. miR-205 upregulation occurred frequently in NECs without lymph node metastases (P = 0.030), whereas such association was not present in ECs. Interestingly, In ECs, miR-200a/miR-141 upregulation occurred frequently in the hormone receptor positive subgroups than the negative subgroups (P < 0.05). Similarly, the expression level of miR-205 was higher in the hormone receptor positive subgroups and the association between miR-205 and PR reached statistical significance (P = 0.024). In contrast, in NECs, a negative correlation was found between miR-200a/miR-141 and ER or PR status. Meanwhile, in ECs, miR-200a upregulation correlated with prolonged survival in the ER positive subgroup (P = 0.046), whereas an inverse trend existed in the ER negative subgroup. Our findings suggest that miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. However, they might behave differently in ECs versus NECs. miR-200a/miR-141 and miR-205 might be associated with hormone receptor status in endometrial cancer and may possess prognostic impacts. PMID:26045795

  17. A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation.

    PubMed

    Hu, Rong; Liu, Wei; Li, Hui; Yang, Li; Chen, Chao; Xia, Zhu-Ying; Guo, Li-Juan; Xie, Hui; Zhou, Hou-De; Wu, Xian-Ping; Luo, Xiang-Hang

    2011-04-01

    Our recent study showed that miR-2861 promotes osteoblast differentiation by targeting histone deacetylase 5, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Here we identified another new microRNA (miRNA) (miR-3960) that played a regulatory role in osteoblast differentiation through a regulatory feedback loop with miR-2861. miR-3960 and miR-2861 were found clustered at the same loci. miR-3960 was transcribed during bone morphogenic protein 2 (BMP2)-induced osteogenesis of ST2 stromal cells. Overexpression of miR-3960 promoted BMP2-induced osteoblastogenesis. However, the inhibition of miR-3960 expression attenuated the osteoblastogenesis. Homeobox A2 (Hoxa2), a repressor of Runx2 expression, was confirmed to be a target of miR-3960. Electrophoretic mobility shift assay and chromatin immunoprecipitation experiments confirmed that Runx2 bound to the promoter of the miR-3960/miR-2861 cluster. Furthermore, overexpression of Runx2 induced miR-3960/miR-2861 transcription, and block of Runx2 expression attenuated BMP2-induced miR-3960/miR-2861 transcription. Here we report that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast differentiation. PMID:21324897

  18. Obtaining miRNA-Target Interaction Information from miRWalk2.0.

    PubMed

    Parveen, Alisha; Gretz, Norbert; Dweep, Harsh

    2016-01-01

    miRWalk2.0 (http://zmf.umm.uni-heidelberg.de/mirwalk2) is a freely accessible, regularly updated comprehensive archive supplying the largest available collection of predicted and experimentally verified miRNA-target interactions, with various novel and unique features to assist the scientific community. Approximately 949 million interactions between 11,748 miRNAs, 308,700 genes, and 68,460 lncRNAs are documented in miRWalk2.0 with 5,146,217 different kinds of identifiers to offer a one-stop site to collect an abundance of information. This article describes a schematic workflow on how to obtain miRNA-target interactions from miRWalk2.0. © 2016 by John Wiley & Sons, Inc. PMID:27603021

  19. The miR-17∼92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1.

    PubMed

    Mian, Yousaf A; Zeleznik-Le, Nancy J

    2016-07-01

    Mixed lineage leukemias have a relatively poor prognosis and arise as a result of translocations between the MLL(KMT2A) gene and one of multiple partner genes. Downstream targets of MLL are aberrantly upregulated and include the developmentally important HOX genes and MEIS1, as well as multiple microRNAs (miRNAs), including the miR-17∼92 cluster. Here we examined the contribution of specific miRNAs to MLL leukemias through knockdown studies utilizing custom anti-microRNA oligonucleotides. Combinatorial treatment against miR-17-5p and miR-19a-3p of the miR-17∼92 cluster dramatically reduces colony forming ability of MLL-fusion containing cell lines relative to non-MLL acute myeloid leukemia (AML) controls. To determine the mechanism by which these miRNAs contribute to leukemia, we validated PKNOX1 as a target of both miR-17-5p and miR-19a-3p. MEIS1 and PKNOX1 are TALE domain proteins that participate in ternary complexes with HOX and PBX partners. Here we establish the competitive relationship between PKNOX1 and MEIS1 in PBX-containing complex formation and determine the antagonistic role of PKNOX1 to leukemia in a murine MLL-AF9 model. These data implicate the miR-17∼92 cluster as part of a regulatory mechanism necessary to maintain MEIS1/HOXA9 -mediated transformation in MLL leukemia, indicating that targeting multiple non-homologous miRNAs may be utilized as a novel therapeutic regimen. PMID:27123834

  20. Anti-Inflammatory Activity of Tanshinone IIA in LPS-Stimulated RAW264.7 Macrophages via miRNAs and TLR4-NF-κB Pathway.

    PubMed

    Fan, Guanwei; Jiang, Xiaorui; Wu, Xiaoyan; Fordjour, Patrick Asare; Miao, Lin; Zhang, Han; Zhu, Yan; Gao, Xiumei

    2016-02-01

    Inflammation is a physiological response to infection or injury and involves the innate and adaptive immune system. Tanshinone IIA (Tan IIA) is a well-known flavonoid that elicits an important therapeutic effect by inhibiting inflammatory response. In this study, we examined whether Tan IIA exerts anti-inflammatory activity and investigated the possible mechanisms, including Toll-like receptor 4 (TLR4)-MyD88-nuclear factor kappa B (NF-κB) signaling pathway and microRNA expression in lipopolysaccharide (LPS)-induced RAW264.7 cells. Tan IIA could attenuate the inflammatory reaction via decreasing cytokine, chemokine, and acute-phase protein production, including GM-CSF, sICAM-1, cxcl-1, MIP-1α, and tumor necrosis factor alpha (TNF-α), analyzed by Proteome profile array in LPS-induced RAW264.7 cells. Concurrently, the messenger RNA (mRNA) expressions of IL-1β, TNF-α, and COX-2 were also significantly reduced by Tan IIA. Additionally, Tan IIA decreased LPS-induced NF-κB activation and downregulated TLR4 and MyD88 protein expression levels. We also observed reduced microRNA-155, miR-147, miR-184, miR-29b, and miR-34c expression levels, while LPS-induced microRNA-105, miR-145a, miR-194, miR-383, miR-132, and miR-451a expression levels were upregulated using microRNA (miRNA) qPCR array. Our results indicate that Tan IIA could exert an anti-inflammatory effect on LPS-induced RAW264.7 cells by decreasing TLR4-MyD88-NF-κB signaling pathway and regulating a series of cytokine production and miRNA expression. PMID:26639663

  1. miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes

    PubMed Central

    Marchand, Lucien; Jalabert, Audrey; Meugnier, Emmanuelle; Van den Hende, Kathleen; Fabien, Nicole; Nicolino, Marc; Madec, Anne-Marie; Thivolet, Charles; Rome, Sophie

    2016-01-01

    Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease. PMID:27314045

  2. Acute malocclusion.

    PubMed

    Dupont, John S

    2006-01-01

    Acute malocclusion can result from disturbances in the maxillary/mandibular tooth relationship. These alterations in the occlusal position can result from high fillings, sinus problems, abscesses, periodontal disease, and moving or erupting teeth. Conditions seen less frequently include acute malocclusions secondary to an event (such as trauma) that make a stable dental relationship an unstable one. Patients can demonstrate any of a number of clinical conditions that interfere with their comfort and ability to function. This article provides information on some of the less familiar causes of acute malocclusion. PMID:16689064

  3. miRNome in myocardial infarction: Future directions and perspective

    PubMed Central

    Boštjančič, Emanuela; Glavač, Damjan

    2014-01-01

    MicroRNAs (miRNAs), which are small and non-coding RNAs, are genome encoded from viruses to humans. They contribute to various developmental, physiological and pathological processes in living organisms. A huge amount of research results revealed that miRNAs regulate these processes also in the heart. miRNAs may have cell-type-specific or tissue-specific expression patterns or may be expressed ubiquitously. Primary studies of miRNA involvement in hypertrophy, heart failure and myocardial infarction analyzed miRNAs that are enriched in or specific for cardiomyocytes; however, growing evidence suggest that other miRNAs, not cardiac or muscle-specific, play a significant role in cardiovascular disease. Abnormal miRNA regulation has been shown to be involved in cardiac diseases, suggesting that miRNAs might affect cardiac structure and function. In this review, we focus on miRNAs that have been found to contribute to the pathogenesis of myocardial infarction (MI) and the response post-MI and characterized as diagnostic, prognostic and therapeutic targets. The majority of these studies were performed using mouse and rat models of MI, with a focus on the identification of basic cellular and molecular pathways involved in MI and in the response post-MI. Much research has also been performed on animal and human plasma samples from MI individuals to identify miRNAs that are possible prognostic and/or diagnostic targets of MI and other MI-related diseases. A large proportion of research is focused on miRNAs as promising therapeutic targets and biomarkers of drug responses and/or stem cell treatment approaches. However, only a few studies have described miRNA expression in human heart tissue following MI. PMID:25276296

  4. Dynamic Alterations of miR-34c Expression in the Hypothalamus of Male Rats after Early Adolescent Traumatic Stress

    PubMed Central

    Li, Chuting; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2016-01-01

    Several types of microRNA (miRNA) overexpression in the brain are associated with stress. One of the targets of miR-34c is the stress-related corticotrophin releasing factor receptor 1 mRNA (CRFR1 mRNA). Here we will probe into the short-term effect and long-term effect of early adolescent traumatic stress on the expression of miR-34c and CRFR1 mRNA. Traumatic stress was established by electric foot shock for six consecutive days using 28-day rats. The anxiety-like behaviors, memory damage, CRFR1 protein, CRFR1 mRNA, and miR-34c expression were detected in our study. The results of our study proved that exposure to acute traumatic stress in early adolescent can cause permanent changes in neural network, resulting in dysregulation of CRFR1 expression and CRFR1 mRNA and miR-34c expression in hypothalamus, anxiety-like behavior, and memory impairment, suggesting that the miR-34c expression in hypothalamus may be an important factor involved in susceptibility to PTSD. PMID:26925271

  5. VEGFA Expression Is Inhibited by Arsenic Trioxide in HUVECs through the Upregulation of Ets-2 and miRNA-126.

    PubMed

    Ge, Hong-Yan; Han, Zhong-Jing; Tian, Pei; Sun, Wen-Jie; Xue, Da-Xi; Bi, Yu; Yang, Zhang-Hui; Liu, Ping

    2015-01-01

    Arsenic trioxide (ATO) has been used to treat patients with acute promyelocytic leukemia. Recently, studies have shown that ATO can induce apoptosis in leukemic cells and blood vessel endothelial cells in a time- and dose-dependent manner through the inhibition of vascular endothelial growth factor A (VEGFA) production. VEGFA is a key factor in angiogenesis initiation. Targeted inhibition of VEGF or VEGFA expression can suppress angiogenesis; however, little is known about the mechanism by which ATO inhibits VEGFA expression. In this study, we investigated the role of miRNA-126 in the mechanism of action of ATO in human umbilical vein endothelial cells (HUVECs). ATO significantly decreased the viability and proliferation of HUVECs and decreased their migration at 48 h. Cell proliferation was inhibited by 50% (IC50) when 5.0 μmol/L ATO was used. ATO treatment induced miR-126 upregulation and HUVEC apoptosis. Transfection with a miR-126 mimic significantly downregulated VEGFA mRNA levels, and transfection with a miR-126 inhibitor significantly upregulated VEGFA mRNA levels. Finally, we showed that ATO treatment upregulated Ets-2 and miR-126 expression in HUVECs. These results demonstrate that ATO inhibits the growth of HUVECs and induces apoptosis by downregulating VEGFA. One mechanism by which this occurs is Ets-2 upregulation, which results in an increase in miR-126 levels and downregulation of VEGFA expression. PMID:26274316

  6. MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

    PubMed

    Asaoka, T; Sotolongo, B; Island, E R; Tryphonopoulos, P; Selvaggi, G; Moon, J; Tekin, A; Amador, A; Levi, D M; Garcia, J; Smith, L; Nishida, S; Weppler, D; Tzakis, A G; Ruiz, P

    2012-02-01

    Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents. PMID:22026534

  7. MiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation Methodology

    PubMed Central

    Karathanasis, Nestoras; Tsamardinos, Ioannis; Poirazi, Panayiota

    2015-01-01

    We address the problem of predicting the position of a miRNA duplex on a microRNA hairpin via the development and application of a novel SVM-based methodology. Our method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM. This is the first model that provides precise information about all four ends of the miRNA duplex. We show that (a) our method outperforms four state-of-the-art tools, namely MaturePred, MiRPara, MatureBayes, MiRdup as well as a Simple Geometric Locator when applied on the same training datasets employed for each tool and evaluated on a common blind test set. (b) In all comparisons, MiRduplexSVM shows superior performance, achieving up to a 60% increase in prediction accuracy for mammalian hairpins and can generalize very well on plant hairpins, without any special optimization. (c) The tool has a number of important applications such as the ability to accurately predict the miRNA or the miRNA*, given the opposite strand of a duplex. Its performance on this task is superior to the 2nts overhang rule commonly used in computational studies and similar to that of a comparative genomic approach, without the need for prior knowledge or the complexity of performing multiple alignments. Finally, it is able to evaluate novel, potential miRNAs found either computationally or experimentally. In relation with recent confidence evaluation methods used in miRBase, MiRduplexSVM was successful in identifying high confidence potential miRNAs. PMID:25961860

  8. Neurotensin Promotes the Development of Colitis and Intestinal Angiogenesis via Hif-1α-miR-210 Signaling.

    PubMed

    Bakirtzi, Kyriaki; Law, Ivy Ka Man; Xue, Xiang; Iliopoulos, Dimitrios; Shah, Yatrik M; Pothoulakis, Charalabos

    2016-05-15

    Neurotensin (NT) via its receptor 1 (NTR1) modulates the development of colitis, decreases HIF-1α/PHD2 interaction, stabilizes and increases HIF-1α transcriptional activity, and promotes intestinal angiogenesis. HIF-1α induces miR-210 expression, whereas miR-210 is strongly upregulated in response to NT in NCM460 human colonic epithelial cells overexpressing NTR1 (NCM460-NTR1). In this study, we examined whether NT activates a NTR1-HIF-1α-miR-210 cascade using in vitro (NCM460-NTR1 cells) and in vivo (transgenic mice overexpressing [HIF-1α-OE] or lacking HIF-1α [HIF-1α-knockout (KO)] in intestinal epithelial cells and mice lacking NTR1 [NTR1-KO]) models. Pretreatment of NCM460-NTR1 cells with the HIF-1α inhibitor PX-478 or silencing of HIF-1α (small interfering HIF-1α) attenuated miR-210 expression in response to NT. Intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS) administration (2-d model) increased colonic miR-210 expression that was significantly reduced in NTR1-KO, HIF-1α-KO mice, and wild-type mice pretreated intracolonically with locked nucleic acid anti-miR-210. In contrast, HIF-1α-OE mice showed increased miR-210 expression at baseline that was further increased following TNBS administration. HIF-1α-OE mice had also exacerbated TNBS-induced neovascularization compared with TNBS-exposed wild-type mice. TNBS-induced neovascularization was attenuated in HIF-1α-KO mice, or mice pretreated intracolonically with anti-miR-210. Intracolonic anti-miR-210 also reduced colitis in response to TNBS (2 d). Importantly, miR-210 expression was increased in tissue samples from ulcerative colitis patients. We conclude that NT exerts its proinflammatory and proangiogenic effects during acute colitis via a NTR1-prolyl hydroxylase 2/HIF-1α-miR-210 signaling pathway. Our results also demonstrate that miR-210 plays a proinflammatory role in the development of colitis. PMID:27076683

  9. The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome.

    PubMed

    Yao, Rui; Ma, Yulan; Du, Youyou; Liao, Mengyang; Li, Huanhuan; Liang, Wei; Yuan, Jing; Ma, Zhijun; Yu, Xian; Xiao, Hong; Liao, Yuhua

    2011-11-01

    MicroRNAs (miRNAs) are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. Immune cells, especially T helper (Th) cells, are critical in the development of atherosclerosis and the onset of acute coronary syndrome (ACS). To assess whether inflammation-related miRNAs (such as miR-155, 146a, 21, 125a-5p, 125b, 31) are involved in the imbalance of Th cell subsets in patients with ACS, we measured the expression of related miRNAs in patients with acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA) and chest pain syndrome (CPS); analyzed the relationship between miRNA expression and the frequency of Th cell subsets; and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells (PBMCs) of patients with ACS. The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%, while the expression of both miR-21 and miR-146a was increased by approximately twofold. The expression patterns of miRNAs in plasma correlated with those in PBMCs, except for miR-21, which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group. We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells (r=-0.896, P<0.01) and that miR-155 was co-expressed with IL-17A in patients with ACS. In conclusion, our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation. PMID:21804579

  10. Serum microRNA181a: Correlates with the intracellular cytokine levels and a potential biomarker for acute graft-versus-host disease.

    PubMed

    Xie, Linna; Zhou, Fang; Liu, Ximin; Fang, Yuan; Yu, Zhe; Song, Ningxia; Kong, Fansheng

    2016-09-01

    The aim of this study was to investigate the clinical relevance of lymphocyte-related serum miRNAs to the pathogenesis of acute graft-versus-host disease (aGVHD) and evaluate the predictive and prognosis value of miRNAs. Consecutive patients who received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in General Hospital of Jinan Military District were enrolled. aGVHD patients were diagnosed and graded clinically, and divided into the training set and the testing set. Blood samples were collected, total RNA was isolated, and RT-PCR was performed for miRNA expression (miR-181a-3p, miR-214-3p and miR-326). Intracellular cytokines levels were assayed by flow cytometry, and the disease specificity assay of miRNAs for aGVHD was detected. A total of 120 patients were admitted. Serum level of miR-181a in aGVHD patients was highly increased and associated with the severity of aGVHD, but not miR-214 and miR-326. Levels of cytokines including IL-2, IL-22, and IL-17a were positively correlated with miR-181a level, while serum IL-13 level was negatively correlated with miR-181a level in aGVHD patients. Moreover, increased miR-181a level was not detected in patients with acute rejection after kidney transplantation or sepsis patients. MiR-181a level was sensitively and specifically increased, especially in severe aGVHD patients. MiR-181a may be a potential biomarker for the identification, diagnosis, and prognosis of aGVHD patients. PMID:27288630

  11. Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome.

    PubMed

    Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

    2010-01-01

    MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs. PMID:21364831

  12. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  13. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  14. Exercise test in acute myocardial infarction.

    PubMed

    Hsi, W L; Lai, J S

    1996-01-01

    Although maximal oxygen consumption (VO2max) and oxygen consumption at anaerobic threshold (VO2AT) were used to measure cardiac function, the clinical significance in acute myocardial infarction (MI) has not been reported. The purpose of this study was to compare VO2max and VO2AT between post-MI patients and healthy men and to correlate the parameters to other clinical measures. Forty-three active healthy men, 44 sedentary healthy men, and 43 post-MI patients were studied using incremental cycle exercise test. Their work rates, oxygen consumption, heart rates, oxygen pulses, ventilation, and other parameters at VO2max and VO2AT were determined with spirometer, gas concentration analyzer, and electrocardiograph. Anaerobic threshold was determined by analyzing the ventilatory parameters. Most of the exercise test parameters at VO2max were greatest in the active men, intermediate in the sedentary men, and least in the post-MI patients (P < 0.01) whereas the rate-pressure products of the active men and sedentary men were not significantly different from each other and were greater than those of the post-MI patients (P < 0.01). In the post-MI patients, VO2max was inversely correlated to the peak serum level of creatine phosphokinase MB isoenzyme (P < 0.01) and associated with extensive infarction (P < 0.05). Most of the parameters at VO2AT were greater in the active men than in the sedentary men (P < 0.01) but not significantly different between the sedentary men and post-MI patients. In the post-MI patients, VO2AT was significantly correlated to left ventricular ejection fraction (P < 0.01) and associated with heart failure (P < 0.05). The results revealed that VO2max and VO2AT had different clinical significance in post-MI patients; VO2max was related to the infarct size, and VO2AT was related to the pumping function of heart. PMID:8777021

  15. The NuMI Neutrino Beam

    DOE PAGESBeta

    Adamson, P.; Anderson, K.; Andrews, M.; Andrews, R.; Anghel, I.; Augustine, D.; Aurisano, A.; Avvakumov, S.; Ayres, D. S.; Baller, B.; et al

    2015-10-20

    Our paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important part of our design details pertaining to individual components is described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

  16. The NuMI neutrino beam

    NASA Astrophysics Data System (ADS)

    Adamson, P.; Anderson, K.; Andrews, M.; Andrews, R.; Anghel, I.; Augustine, D.; Aurisano, A.; Avvakumov, S.; Ayres, D. S.; Baller, B.; Barish, B.; Barr, G.; Barrett, W. L.; Bernstein, R. H.; Biggs, J.; Bishai, M.; Blake, A.; Bocean, V.; Bock, G. J.; Boehnlein, D. J.; Bogert, D.; Bourkland, K.; Cao, S. V.; Castromonte, C. M.; Childress, S.; Choudhary, B. C.; Coelho, J. A. B.; Cobb, J. H.; Corwin, L.; Crane, D.; Cravens, J. P.; Cronin-Hennessy, D.; Ducar, R. J.; De Jong, J. K.; Devan, A. V.; Devenish, N. E.; Diwan, M. V.; Erwin, A. R.; Escobar, C. O.; Evans, J. J.; Falk, E.; Feldman, G. J.; Fields, T. H.; Ford, R.; Frohne, M. V.; Gallagher, H. R.; Garkusha, V.; Gomes, R. A.; Goodman, M. C.; Gouffon, P.; Graf, N.; Gran, R.; Grossman, N.; Grzelak, K.; Habig, A.; Hahn, S. R.; Harding, D.; Harris, D.; Harris, P. G.; Hartnell, J.; Hatcher, R.; Hays, S.; Heller, K.; Holin, A.; Huang, J.; Hylen, J.; Ibrahim, A.; Indurthy, D.; Irwin, G. M.; Isvan, Z.; Jaffe, D. E.; James, C.; Jensen, D.; Johnstone, J.; Kafka, T.; Kasahara, S. M. S.; Koizumi, G.; Kopp, S.; Kordosky, M.; Kreymer, A.; Lang, K.; Laughton, C.; Lefeuvre, G.; Ling, J.; Litchfield, P. J.; Loiacono, L.; Lucas, P.; Mann, W. A.; Marchionni, A.; Marshak, M. L.; Mayer, N.; McGivern, C.; Medeiros, M. M.; Mehdiyev, R.; Meier, J. R.; Messier, M. D.; Michael, D. G.; Milburn, R. H.; Miller, J. L.; Miller, W. H.; Mishra, S. R.; Moed Sher, S.; Moore, C. D.; Morfín, J.; Mualem, L.; Mufson, S.; Murgia, S.; Murtagh, M.; Musser, J.; Naples, D.; Nelson, J. K.; Newman, H. B.; Nichol, R. J.; Nowak, J. A.; O`Connor, J.; Oliver, W. P.; Olsen, M.; Orchanian, M.; Osprey, S.; Pahlka, R. B.; Paley, J.; Para, A.; Patterson, R. B.; Patzak, T.; Pavlović, Ž.; Pawloski, G.; Perch, A.; Peterson, E. A.; Petyt, D. A.; Pfützner, M. M.; Phan-Budd, S.; Plunkett, R. K.; Poonthottathil, N.; Prieto, P.; Pushka, D.; Qiu, X.; Radovic, A.; Rameika, R. A.; Ratchford, J.; Rebel, B.; Reilly, R.; Rosenfeld, C.; Rubin, H. A.; Ruddick, K.; Sanchez, M. C.; Saoulidou, N.; Sauer, L.; Schneps, J.; Schoo, D.; Schreckenberger, A.; Schreiner, P.; Shanahan, P.; Sharma, R.; Smart, W.; Smith, C.; Sousa, A.; Stefanik, A.; Tagg, N.; Talaga, R. L.; Tassotto, G.; Thomas, J.; Thompson, J.; Thomson, M. A.; Tian, X.; Timmons, A.; Tinsley, D.; Tognini, S. C.; Toner, R.; Torretta, D.; Trostin, I.; Tzanakos, G.; Urheim, J.; Vahle, P.; Vaziri, K.; Villegas, E.; Viren, B.; Vogel, G.; Webber, R. C.; Weber, A.; Webb, R. C.; Wehmann, A.; White, C.; Whitehead, L.; Whitehead, L. H.; Wojcicki, S. G.; Wong-Squires, M. L.; Yang, T.; Yumiceva, F. X.; Zarucheisky, V.; Zwaska, R.

    2016-01-01

    This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

  17. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  18. Tumor-suppressing roles of miR-214 and miR-218 in breast cancer

    PubMed Central

    LIU, BO; TIAN, YANFENG; LI, FANG; ZHAO, ZENGREN; JIANG, XIA; ZHAI, CONGJIE; HAN, XIAODONG; ZHANG, LIKE

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are key post-transcriptional regulators of gene expression. MicroRNA-214 (miR-214) and microRNA-218 (miR-218) have shown the function of tumor suppressors in various types of human cancers. However, the biological functions of miR-214 and miR-218 in breast cancer have not been elucidated completely. The present study evaluated the expression and biological function of miR-214 and miR-218 in human breast cancer. Our results revealed that the expression of miR-214 and miR-218 were significantly decreased in breast cancer tissues compared with adjacent tissues. The aberrant expression of miR-214 and miR-218 were negatively associated with Ki-67, and the miR-218 expression was positively associated with progesterone receptor (PR) in breast cancer tissues. In vitro, the cell proliferation and migration were decreased, cell apoptosis was induced, and cell cycle was also disturbed in miR-214 or miR-218 overexpressed breast cancer cells. Our results demonstrated that miR-214 and miR-218 function as tumor suppressors in breast cancer, and may become biomarkers and potential therapeutic targets in breast cancer. PMID:27109339

  19. Tumor-suppressing roles of miR-214 and miR-218 in breast cancer.

    PubMed

    Liu, Bo; Tian, Yanfeng; Li, Fang; Zhao, Zengren; Jiang, Xia; Zhai, Congjie; Han, Xiaodong; Zhang, Like

    2016-06-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are key post-transcriptional regulators of gene expression. MicroRNA-214 (miR-214) and microRNA-218 (miR-218) have shown the function of tumor suppressors in various types of human cancers. However, the biological functions of miR-214 and miR-218 in breast cancer have not been elucidated completely. The present study evaluated the expression and biological function of miR-214 and miR-218 in human breast cancer. Our results revealed that the expression of miR-214 and miR-218 were significantly decreased in breast cancer tissues compared with adjacent tissues. The aberrant expression of miR-214 and miR-218 were negatively associated with Ki-67, and the miR-218 expression was positively associated with progesterone receptor (PR) in breast cancer tissues. In vitro, the cell proliferation and migration were decreased, cell apoptosis was induced, and cell cycle was also disturbed in miR-214 or miR-218 overexpressed breast cancer cells. Our results demonstrated that miR-214 and miR-218 function as tumor suppressors in breast cancer, and may become biomarkers and potential therapeutic targets in breast cancer. PMID:27109339

  20. Generalizing Screen Inferiority--Does the Medium, Screen versus Paper, Affect Performance Even with Brief Tasks?

    ERIC Educational Resources Information Center

    Sidi, Yael; Ophir, Yael; Ackerman, Rakefet

    2016-01-01

    Screen inferiority in performance and metacognitive processes has been repeatedly found with text learning. Common explanations for screen inferiority relate to technological and physiological disadvantages associated with extensive reading on screen. However, recent studies point to lesser recruitment of mental effort on screen than on paper.…

  1. Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA-Seq

    PubMed Central

    Sun, Hongzheng; Peng, Ting; Zhao, Yafan; Du, Yanxiu; Zhang, Jing; Li, Junzhou; Xin, Zeyu; Zhao, Quanzhi

    2015-01-01

    Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID:26355995

  2. Does the Left Inferior Longitudinal Fasciculus Play a Role in Language? A Brain Stimulation Study

    ERIC Educational Resources Information Center

    Mandonnet, Emmanuel; Nouet, Aurelien; Gatignol, Peggy; Capelle, Laurent; Duffau, Hugues

    2007-01-01

    Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by…

  3. Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA-Seq.

    PubMed

    Sun, Hongzheng; Peng, Ting; Zhao, Yafan; Du, Yanxiu; Zhang, Jing; Li, Junzhou; Xin, Zeyu; Zhao, Quanzhi

    2015-01-01

    Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID:26355995

  4. Telomere Length, TERT, and miRNA Expression.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Pellatt, Andrew J; Wolff, Roger K; Mullany, Lila E

    2016-01-01

    It has been proposed that miRNAs are involved in the control of telomeres. We test that hypothesis by examining the association between miRNAs and telomere length (TL). Additionally, we evaluate if genetic variation in telomerase reverse transcriptase (TERT) is associated with miRNA expression levels. We use data from a population-based study of colorectal cancer (CRC), where we have previously shown associations between TL and TERT and CRC, to test associations between TL and miRNA expression and TERT and miRNA expression. To gain insight into functions of miRNAs associated with TERT we tested linear associations between miRNAs and their targeted gene mRNAs. An Agilent platform that contained information on over 2000 miRNAs was used. TL was measured using a multiplexed quantitative PCR (qPCR). RNAseq was used to assess gene expression. Our sample consisted of 1152 individuals with SNP data and miRNA expression data; 363 individuals with both TL and miRNA; and 148 individuals with miRNA and mRNA data. Thirty-three miRNAs were directly associated with TL after adjusting for age and sex (false discovery rate (FDR) of 0.05). TERT rs2736118 was associated with differences in miRNA expression between carcinoma and normal colonic mucosa for 75 miRNAs (FDR <0.05). Genes regulated by these miRNAs, as indicated by mRNA/miRNA associations, were associated with major signaling pathways beyond their TL-related functions, including PTEN, and PI3K/AKT signaling. Our data support a direct association between miRNAs and TL; differences in miRNA expression levels by TERT genotype were observed. Based on miRNA and targeted mRNA associations our data suggest that TERT is involved in non-TL-related functions by acting through altered miRNA expression. PMID:27627813

  5. Addendum to NuMI shielding assessment

    SciTech Connect

    Vaziri, Kamran; /Fermilab

    2007-10-01

    The original safety assessment and the Safety Envelope for the NuMI beam line corresponds to 400 kW of beam power. The Main Injector is currently capable of and approved for producing 500 kW of beam power2. However, operation of the NuMI beam line at 400 kW of power brings up the possibility of an occasional excursion above 400 kW due to better than usual tuning in one of the machines upstream of the NuMI beam line. An excursion above the DOE approved Safety Envelope will constitute a safety violation. The purpose of this addendum is to evaluate the radiological issues and modifications required to operate the NuMI beam line at 500 kW. This upgrade will allow 400 kW operations with a reasonable safety margin. Configuration of the NuMI beam line, boundaries, safety system and the methodologies used for the calculations are as described in the original NuMI SAD. While most of the calculations presented in the original shielding assessment were based on Monte Carlo simulations, which were based on the design geometries, most of the results presented in this addendum are based on the measurements conducted by the AD ES&H radiation safety group.

  6. Prediction of miRNA targets.

    PubMed

    Oulas, Anastasis; Karathanasis, Nestoras; Louloupi, Annita; Pavlopoulos, Georgios A; Poirazi, Panayiota; Kalantidis, Kriton; Iliopoulos, Ioannis

    2015-01-01

    Computational methods for miRNA target prediction are currently undergoing extensive review and evaluation. There is still a great need for improvement of these tools and bioinformatics approaches are looking towards high-throughput experiments in order to validate predictions. The combination of large-scale techniques with computational tools will not only provide greater credence to computational predictions but also lead to the better understanding of specific biological questions. Current miRNA target prediction tools utilize probabilistic learning algorithms, machine learning methods and even empirical biologically defined rules in order to build models based on experimentally verified miRNA targets. Large-scale protein downregulation assays and next-generation sequencing (NGS) are now being used to validate methodologies and compare the performance of existing tools. Tools that exhibit greater correlation between computational predictions and protein downregulation or RNA downregulation are considered the state of the art. Moreover, efficiency in prediction of miRNA targets that are concurrently verified experimentally provides additional validity to computational predictions and further highlights the competitive advantage of specific tools and their efficacy in extracting biologically significant results. In this review paper, we discuss the computational methods for miRNA target prediction and provide a detailed comparison of methodologies and features utilized by each specific tool. Moreover, we provide an overview of current state-of-the-art high-throughput methods used in miRNA target prediction. PMID:25577381

  7. Evaluation of the Differences of Myocardial Fibers between Acute and Chronic Myocardial Infarction: Application of Diffusion Tensor Magnetic Resonance Imaging in a Rhesus Monkey Model

    PubMed Central

    Wang, Yuqing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie

    2016-01-01

    Objective To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Materials and Methods Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Results Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10-4 mm2/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10-4mm2/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Conclusion Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models. PMID:27587961

  8. Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients

    PubMed Central

    Stückrath, Isabel; Rack, Brigitte; Janni, Wolfgang; Jäger, Bernadette; Pantel, Klaus; Schwarzenbach, Heidi

    2015-01-01

    Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer. Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR. Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells. Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression. PMID:26033453

  9. Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients.

    PubMed

    Stückrath, Isabel; Rack, Brigitte; Janni, Wolfgang; Jäger, Bernadette; Pantel, Klaus; Schwarzenbach, Heidi

    2015-05-30

    Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer.Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR.Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells.Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression. PMID:26033453

  10. Aberrant expression of miR-127, miR-21 and miR-16 in placentas of deceased cloned sheep.

    PubMed

    Ni, Wei; You, Shuang; Cao, Yang; Li, Cunyuan; Wei, Junchuang; Wang, Dawei; Qiao, Jun; Zhao, Xinxia; Hu, Shengwei; Quan, Renzhe

    2016-04-01

    Placental deficiencies are associated with developmental abnormalities of animal produced by somatic cell nuclear transfer (SCNT). It is reported that aberrant expression of microRNAs (miRNAs) in the common placenta is associated with fetal growth restriction and placental deficiencies. However, an understanding of the expression and function of miRNAs in the placentas of cloned animal is lacking. In this study, we characterized the expression of five growth-associated miRNAs (miR-127, miR-16, miR-21, miR-93 and miR-182) in placentas of deceased transgenic cloned sheep (deceased group, n=7), live transgenic cloned sheep (live group, n=5) and conventionally produced sheep (control group, n=10). Expression levels of miR-127 (P<0.01), miR-21 (P<0.01) and miR-16 (P<0.05) were significantly up-regulated in the placentas of deceased group compared to that of control group. In contrast, the expression of these miRNAs was largely normal in the placentas of live group, except for the expression of miR-21. Furthermore, we confirmed that retrotransposon-like gene (Rtl1), a key gene in placental development, was down-regulated by miR-127 as a target in placenta cells. Our results suggested that the abnormal expression of miR-127, miR-21 and miR-16 in placentas of deceased sheep, through dysregulation of target genes, may result in developmental deficiencies of transgenic cloned sheep. PMID:27033933

  11. Misprocessing and functional arrest of microRNAs by miR-Pirate: roles of miR-378 and miR-17.

    PubMed

    Deng, Zhaoqun; Yang, Xiangling; Fang, Ling; Rutnam, Zina J; Yang, Burton B

    2013-03-01

    miRNAs (microRNAs) are short non-coding RNAs that can regulate gene expression in cancer development, which makes them valuable targets for therapeutic intervention. In the present study we report on an approach that can not only arrest the functions of mature miRNAs by binding to them, but it can also induce the 'mis-processing' of the target miRNA, producing a non-functional truncated miRNA. This approach involves generating an expression construct that produces an RNA fragment with 16 repeat sequences. The construct is named miR-Pirate (miRNA-interacting RNA-producing imperfect RNA and tangling endogenous miRNA). The transcript of the construct contained mismatches to the seed region, and thus it would not target the potential targets of the miRNA under study. The homology of the construct is sufficiently high, allowing the transcript to block miRNA functions. The functions of the construct were validated in cell cultures, in tumour formation assays and in transgenic mice stably expressing this construct. To explore the possibility of adopting this approach in gene therapy, we transfected cells with synthetic miR-Pirate and obtained the results we expected. The miR-Pirate, expressed by the construct or synthesized chemically, was found to be able to specifically pirate and silence a mature miRNA through its dual roles and thus could be clinically applied for miRNA intervention. PMID:23210454

  12. Role of miR-1 and miR-133a in myocardial ischemic postconditioning

    PubMed Central

    2011-01-01

    Background Ischemic postconditioning (IPost) has aroused much attention since 2003 when it was firstly reported. The role of microRNAs (miRNAs or miRs) in IPost has rarely been reported. The present study was undertaken to investigate whether miRNAs were involved in the protective effect of IPost against myocardial ischemia-reperfusion (IR) injury and the probable mechanisms involved. Methods Thirty SD rats weighing 250-300 g were equally randomized to three groups: Control group, where the rats were treated with thoracotomy only; IR group, where the rats were treated with ischemia for 60 min and reperfusion for 180 min; and IPost group, where the rats were treated with 3 cycles of transient IR just before reperfusion. The extent of myocardial infarction, LDH and CK activities were measured immediately after treatment. Myocardial apoptosis was detected by TUNEL assay. The myocardial tissue was collected after IR or IPost stimulation to evaluate the miRNAs expression level by miRNA-microarray and quantitative real-time RT-PCR. Real-time PCR was conducted to identify changes in mRNA expression of apoptosis-related genes such as Bcl-2, Bax and Caspase-9 (CASP9), and Western blot was used to compare the protein expression level of CASP9 in the three groups. The miRNA mimics and anti-miRNA oligonucleotides (AMO) were transferred into the cultured neonatal cardiomyocytes and myocardium before they were treated with IR. The effect of miRNAs on apoptosis was determined by flow cytometry and TUNEL assay. CASP9, as one of the candidate target of miR-133a, was compared during IR after the miR-133a mimic or AMO-133a was transferred into the myocardium. Results IPost reduced the IR-induced infarct size of the left ventricle, and decreased CK and LDH levels. TUNEL assay showed that myocardial apoptosis was attenuated by IPost compared with IR. MiRNA-microarray and RT-PCR showed that myocardial-specific miR-1 and miR-133a were down-regulated by IR, and up-regulated by IPost

  13. The inferior cochlear vein: surgical aspects in cochlear implantation.

    PubMed

    Guo, Rui; Zhang, HongLei; Chen, Wei; Zhu, XiaoQuan; Liu, Wei; Rask-Andersen, Helge

    2016-02-01

    The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively. PMID:25700831

  14. Dopaminergic Input to the Inferior Colliculus in Mice.

    PubMed

    Nevue, Alexander A; Elde, Cameron J; Perkel, David J; Portfors, Christine V

    2015-01-01

    The response of sensory neurons to stimuli can be modulated by a variety of factors including attention, emotion, behavioral context, and disorders involving neuromodulatory systems. For example, patients with Parkinson's disease (PD) have disordered speech processing, suggesting that dopamine alters normal representation of these salient sounds. Understanding the mechanisms by which dopamine modulates auditory processing is thus an important goal. The principal auditory midbrain nucleus, the inferior colliculus (IC), is a likely location for dopaminergic modulation of auditory processing because it contains dopamine receptors and nerve terminals immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. However, the sources of dopaminergic input to the IC are unknown. In this study, we iontophoretically injected a retrograde tracer into the IC of mice and then stained the tissue for TH. We also immunostained for dopamine beta-hydroxylase (DBH), an enzyme critical for the conversion of dopamine to norepinephrine, to differentiate between dopaminergic and noradrenergic inputs. Retrogradely labeled neurons that were positive for TH were seen bilaterally, with strong ipsilateral dominance, in the subparafascicular thalamic nucleus (SPF). All retrogradely labeled neurons that we observed in other brain regions were TH-negative. Projections from the SPF were confirmed using an anterograde tracer, revealing TH-positive and DBH-negative anterogradely labeled fibers and terminals in the IC. While the functional role of this dopaminergic input to the IC is not yet known, it provides a potential mechanism for context dependent modulation of auditory processing. PMID:26834578

  15. Tinnitus-Related Changes in the Inferior Colliculus

    PubMed Central

    Berger, Joel I.; Coomber, Ben

    2015-01-01

    Tinnitus is highly complex, diverse, and difficult to treat, in part due to the fact that the underlying causes and mechanisms remain elusive. Tinnitus is generated within the auditory brain; however, consolidating our understanding of tinnitus pathophysiology is difficult due to the diversity of reported effects and the variety of implicated brain nuclei. Here, we focus on the inferior colliculus (IC), a midbrain structure that integrates the vast majority of ascending auditory information and projects via the thalamus to the auditory cortex. The IC is also a point of convergence for corticofugal input and input originating outside the auditory pathway. We review the evidence, from both studies with human subjects and from animal models, for the contribution the IC makes to tinnitus. Changes in the IC, caused by either noise exposure or drug administration, involve fundamental, heterogeneous alterations in the balance of excitation and inhibition. However, differences between hearing loss-induced pathology and tinnitus-related pathology are not well understood. Moreover, variability in tinnitus induction methodology has a significant impact on subsequent neural and behavioral changes, which could explain some of the seemingly contradictory data. Nonetheless, the IC is likely involved in the generation and persistence of tinnitus perception. PMID:25870582

  16. Serotonin shifts first-spike latencies of inferior colliculus neurons.

    PubMed

    Hurley, Laura M; Pollak, George D

    2005-08-24

    Many studies of neuromodulators have focused on changes in the magnitudes of neural responses, but fewer studies have examined neuromodulator effects on response latency. Across sensory systems, response latency is important for encoding not only the temporal structure but also the identity of stimuli. In the auditory system, latency is a fundamental response property that varies with many features of sound, including intensity, frequency, and duration. To determine the extent of neuromodulatory regulation of latency within the inferior colliculus (IC), a midbrain auditory nexus, the effects of iontophoretically applied serotonin on first-spike latencies were characterized in the IC of the Mexican free-tailed bat. Serotonin significantly altered the first-spike latencies in response to tones in 24% of IC neurons, usually increasing, but sometimes decreasing, latency. Serotonin-evoked changes in latency and spike count were not always correlated but sometimes occurred independently within individual neurons. Furthermore, in some neurons, the size of serotonin-evoked latency shifts depended on the frequency or intensity of the stimulus, as reported previously for serotonin-evoked changes in spike count. These results support the general conclusion that changes in latency are an important part of the neuromodulatory repertoire of serotonin within the auditory system and show that serotonin can change latency either in conjunction with broad changes in other aspects of neuronal excitability or in highly specific ways. PMID:16120790

  17. Obstruction increases activation in the right inferior frontal gyrus.

    PubMed

    Liu, Tao; Saito, Hirofumi; Oi, Misato

    2016-08-01

    The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions. PMID:26366676

  18. Effects of inferior olive lesion on fear-conditioned bradycardia

    PubMed Central

    Kotajima, Hiroko; Sakai, Kazuhisa; Hashikawa, Tsutomu

    2014-01-01

    The inferior olive (IO) sends excitatory inputs to the cerebellar cortex and cerebellar nuclei through the climbing fibers. In eyeblink conditioning, a model of motor learning, the inactivation of or a lesion in the IO impairs the acquisition or expression of conditioned eyeblink responses. Additionally, climbing fibers originating from the IO are believed to transmit the unconditioned stimulus to the cerebellum in eyeblink conditioning. Studies using fear-conditioned bradycardia showed that the cerebellum is associated with adaptive control of heart rate. However, the role of inputs from the IO to the cerebellum in fear-conditioned bradycardia has not yet been investigated. To examine this possible role, we tested fear-conditioned bradycardia in mice by selective disruption of the IO using 3-acetylpyridine. In a rotarod test, mice with an IO lesion were unable to remain on the rod. The number of neurons of IO nuclei in these mice was decreased to ∼40% compared with control mice. Mice with an IO lesion did not show changes in the mean heart rate or in heart rate responses to a conditioned stimulus, or in their responses to a painful stimulus in a tail-flick test. However, they did show impairment of the acquisition/expression of conditioned bradycardia and attenuation of heart rate responses to a pain stimulus used as an unconditioned stimulus. These results indicate that the IO inputs to the cerebellum play a key role in the acquisition/expression of conditioned bradycardia. PMID:24784584

  19. Right inferior longitudinal fasciculus lesions disrupt visual-emotional integration.

    PubMed

    Fischer, David B; Perez, David L; Prasad, Sashank; Rigolo, Laura; O'Donnell, Lauren; Acar, Diler; Meadows, Mary-Ellen; Baslet, Gaston; Boes, Aaron D; Golby, Alexandra J; Dworetzky, Barbara A

    2016-06-01

    The mechanism by which the brain integrates visual and emotional information remains incompletely understood, and can be studied through focal lesions that selectively disrupt this process. To date, three reported cases of visual hypoemotionality, a vision-specific form of derealization, have resulted from lesions of the temporo-occipital junction. We present a fourth case of this rare phenomenon, and investigate the role of the inferior longitudinal fasciculus (ILF) in the underlying pathophysiology. A 50-year-old right-handed male was found to have a right medial temporal lobe tumor following new-onset seizures. Interstitial laser ablation of the lesion was complicated by a right temporo-parieto-occipital intraparenchymal hemorrhage. The patient subsequently experienced emotional estrangement from visual stimuli. A lesion overlap analysis was conducted to assess involvement of the ILF by this patient's lesion and those of the three previously described cases, and diffusion tensor imaging was acquired in our case to further investigate ILF disruption. All four lesions specifically overlapped with the expected trajectory of the right ILF, and diminished structural integrity of the right ILF was observed in our case. These findings implicate the ILF in visual hypoemotionality, suggesting that the ILF is critical for integrating visual information with its emotional content. PMID:26940563

  20. Visual modulation of auditory responses in the owl inferior colliculus.

    PubMed

    Bergan, Joseph F; Knudsen, Eric I

    2009-06-01

    The barn owl's central auditory system creates a map of auditory space in the external nucleus of the inferior colliculus (ICX). Although the crucial role visual experience plays in the formation and maintenance of this auditory space map is well established, the mechanism by which vision influences ICX responses remains unclear. Surprisingly, previous experiments have found that in the absence of extensive pharmacological manipulation, visual stimuli do not drive neural responses in the ICX. Here we investigated the influence of dynamic visual stimuli on auditory responses in the ICX. We show that a salient visual stimulus, when coincident with an auditory stimulus, can modulate auditory responses in the ICX even though the same visual stimulus may elicit no neural responses when presented alone. For each ICX neuron, the most effective auditory and visual stimuli were located in the same region of space. In addition, the magnitude of the visual modulation of auditory responses was dependent on the context of the stimulus presentation with novel visual stimuli eliciting consistently larger response modulations than frequently presented visual stimuli. Thus the visual modulation of ICX responses is dependent on the characteristics of the visual stimulus as well as on the spatial and temporal correspondence of the auditory and visual stimuli. These results demonstrate moment-to-moment visual enhancements of auditory responsiveness that, in the short-term, increase auditory responses to salient bimodal stimuli and in the long-term could serve to instruct the adaptive auditory plasticity necessary to maintain accurate auditory orienting behavior. PMID:19321633

  1. Advanced Techniques for Removal of Retrievable Inferior Vena Cava Filters

    SciTech Connect

    Iliescu, Bogdan; Haskal, Ziv J.

    2012-08-15

    Inferior vena cava (IVC) filters have proven valuable for the prevention of primary or recurrent pulmonary embolism in selected patients with or at high risk for venous thromboembolic disease. Their use has become commonplace, and the numbers implanted increase annually. During the last 3 years, in the United States, the percentage of annually placed optional filters, i.e., filters than can remain as permanent filters or potentially be retrieved, has consistently exceeded that of permanent filters. In parallel, the complications of long- or short-term filtration have become increasingly evident to physicians, regulatory agencies, and the public. Most filter removals are uneventful, with a high degree of success. When routine filter-retrieval techniques prove unsuccessful, progressively more advanced tools and skill sets must be used to enhance filter-retrieval success. These techniques should be used with caution to avoid damage to the filter or cava during IVC retrieval. This review describes the complex techniques for filter retrieval, including use of additional snares, guidewires, angioplasty balloons, and mechanical and thermal approaches as well as illustrates their specific application.

  2. Direction Selectivity Mediated by Adaptation in the Owl's Inferior Colliculus

    PubMed Central

    Peña, José Luis

    2013-01-01

    Motion direction is a crucial cue for predicting future states in natural scenes. In the auditory system, the mechanisms that confer direction selectivity to neurons are not well understood. Neither is it known whether sound motion is encoded independently of stationary sound location. Here we investigated these questions in neurons of the owl's external nucleus of the inferior colliculus, where auditory space is represented in a map. Using a high-density speaker array, we show that the preferred direction and the degree of direction selectivity can be predicted by response adaptation to sounds moving over asymmetric spatial receptive fields. At the population level, we found that preference for sounds moving toward frontal space increased with eccentricity in spatial tuning. This distribution was consistent with larger receptive-field asymmetry in neurons tuned to more peripheral auditory space. A model of suppression based on spatiotemporal summation predicted the observations. Thus, response adaptation and receptive-field shape can explain direction selectivity to acoustic motion and an orderly distribution of preferred direction. PMID:24305813

  3. Effect of Preoperative Pain on Inferior Alveolar Nerve Block

    PubMed Central

    Aggarwal, Vivek; Singla, Mamta; Subbiya, Arunajatesan; Vivekanandhan, Paramasivam; Sharma, Vikram; Sharma, Ritu; Prakash, Venkatachalam; Geethapriya, Nagarajan

    2015-01-01

    The present study tested the hypothesis that the amount and severity of preoperative pain will affect the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. One-hundred seventy-seven adult volunteer subjects, actively experiencing pain in a mandibular molar, participated in this prospective double-blind study carried out at 2 different centers. The patients were classified into 3 groups on the basis of severity of preoperative pain: mild, 1–54 mm on the Heft-Parker visual analog scale (HP VAS); moderate, 55–114 mm; and severe, greater than 114 mm. After IANB with 1.8 mL of 2% lidocaine, endodontic access preparation was initiated. Pain during treatment was recorded using the HP VAS. The primary outcome measure was the ability to undertake pulp access and canal instrumentation with no or mild pain. The success rates were statistically analyzed by multiple logistic regression test. There was a significant difference between the mild and severe preoperative pain group (P = .03). There was a positive correlation between the values of preoperative and intraoperative pain (r = .2 and .4 at 2 centers). The amount of preoperative pain can affect the anesthetic success rates of IANB in patients with symptomatic irreversible pulpitis. PMID:26650491

  4. Inferior vena cava resection with hepatectomy: challenging but justified

    PubMed Central

    Malde, Deep J; Khan, Aamir; Prasad, K Rajendra; Toogood, Giles J; Lodge, J Peter A

    2011-01-01

    Objective The aim of this study was to evaluate the clinical outcome of hepatectomy combined with inferior vena cava (IVC) resection and reconstruction for treatment of invasive liver tumours. Methods From February 1995 to September 2010, 2146 patients underwent liver resections in our hospital's hepatopancreatobiliary unit. Of these, 35 (1.6%) patients underwent hepatectomy with IVC resection. These patients were included in this study. Data were analysed from a prospectively collected database. Results Resections were carried out for colorectal liver metastasis (CRLM) (n = 21), hepatocellular carcinoma (n = 6), cholangiocarcinoma (n = 3) and other conditions (n = 5). Resections were carried out with total vascular occlusion in 34 patients and without in one patient. In situ hypothermic perfusion was performed in 13 patients; the ante situm technique was used in three patients, and ex vivo resection was used in six patients. There were four early deaths from multiple organ failure. Postoperative complications occurred in 14 patients, three of whom required re-operation. Median overall survival was 29 months and cumulative 5-year survival was 37.7%. Rates of 1-, 2- and 5-year survival were 75.9%, 58.7% and 19.6%, respectively, in CRLM patients. Conclusions Aggressive surgical management of liver tumours with IVC involvement offers the only hope for cure in selected patients. Resection by specialist teams affords acceptable perioperative morbidity and mortality rates. PMID:21999594

  5. Dopaminergic Input to the Inferior Colliculus in Mice

    PubMed Central

    Nevue, Alexander A.; Elde, Cameron J.; Perkel, David J.; Portfors, Christine V.

    2016-01-01

    The response of sensory neurons to stimuli can be modulated by a variety of factors including attention, emotion, behavioral context, and disorders involving neuromodulatory systems. For example, patients with Parkinson’s disease (PD) have disordered speech processing, suggesting that dopamine alters normal representation of these salient sounds. Understanding the mechanisms by which dopamine modulates auditory processing is thus an important goal. The principal auditory midbrain nucleus, the inferior colliculus (IC), is a likely location for dopaminergic modulation of auditory processing because it contains dopamine receptors and nerve terminals immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. However, the sources of dopaminergic input to the IC are unknown. In this study, we iontophoretically injected a retrograde tracer into the IC of mice and then stained the tissue for TH. We also immunostained for dopamine beta-hydroxylase (DBH), an enzyme critical for the conversion of dopamine to norepinephrine, to differentiate between dopaminergic and noradrenergic inputs. Retrogradely labeled neurons that were positive for TH were seen bilaterally, with strong ipsilateral dominance, in the subparafascicular thalamic nucleus (SPF). All retrogradely labeled neurons that we observed in other brain regions were TH-negative. Projections from the SPF were confirmed using an anterograde tracer, revealing TH-positive and DBH-negative anterogradely labeled fibers and terminals in the IC. While the functional role of this dopaminergic input to the IC is not yet known, it provides a potential mechanism for context dependent modulation of auditory processing. PMID:26834578

  6. Functional role of the human inferior colliculus in binaural hearing.

    PubMed

    Litovsky, Ruth Y; Fligor, Brian J; Tramo, Mark J

    2002-03-01

    Psychophysical experiments were carried out in a rare case involving a 48 year old man (RJC) with a small traumatic hemorrhage of the right dorsal midbrain, including the inferior colliculus (IC). RJC had normal audiograms bilaterally, but there was a marked decrease in wave V amplitude on click-evoked brainstem auditory evoked potentials following left ear stimulation. RJC demonstrated a deficit in sound localization identification when the loudspeakers lay within the auditory hemifield contralateral to his IC lesion. Errors showed a consistent bias towards the hemifield ipsilateral to the lesion. Echo suppression was abnormally weak compared with that seen in control subjects, but only for sources contralateral to the lesion. Finally, speech intelligibility tests showed normal ability to benefit from spatial separation of target and competing speech sources. These results suggest that: (1) localizing sounds within a given hemifield relies on the integrity of the contralateral IC, (2) unilateral IC lesions give the illusion that sound sources in the 'bad' hemifield are displaced towards the 'good' hemifield, (3) the IC mediates aspects of echo suppression, and (4) lesion in the IC does not impede spatial release from masking in speech intelligibility, possibly due to that ability being more heavily mediated by cortical regions. PMID:12031527

  7. Effect of Preoperative Pain on Inferior Alveolar Nerve Block.

    PubMed

    Aggarwal, Vivek; Singla, Mamta; Subbiya, Arunajatesan; Vivekanandhan, Paramasivam; Sharma, Vikram; Sharma, Ritu; Prakash, Venkatachalam; Geethapriya, Nagarajan

    2015-01-01

    The present study tested the hypothesis that the amount and severity of preoperative pain will affect the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. One-hundred seventy-seven adult volunteer subjects, actively experiencing pain in a mandibular molar, participated in this prospective double-blind study carried out at 2 different centers. The patients were classified into 3 groups on the basis of severity of preoperative pain: mild, 1-54 mm on the Heft-Parker visual analog scale (HP VAS); moderate, 55-114 mm; and severe, greater than 114 mm. After IANB with 1.8 mL of 2% lidocaine, endodontic access preparation was initiated. Pain during treatment was recorded using the HP VAS. The primary outcome measure was the ability to undertake pulp access and canal instrumentation with no or mild pain. The success rates were statistically analyzed by multiple logistic regression test. There was a significant difference between the mild and severe preoperative pain group (P = .03). There was a positive correlation between the values of preoperative and intraoperative pain (r = .2 and .4 at 2 centers). The amount of preoperative pain can affect the anesthetic success rates of IANB in patients with symptomatic irreversible pulpitis. PMID:26650491

  8. Surgical treatment of painful lesions of the inferior alveolar nerve.

    PubMed

    Biglioli, Federico; Allevi, Fabiana; Lozza, Alessandro

    2015-10-01

    Nerve-related complications are being reported with increasing frequency following oral and dental surgery, and typically involve the inferior alveolar nerve (IAN). We assess herein the etiology of neuropathic pain related to IAN injuries, and describe the various surgical treatment techniques available. Between 2007 and 2013, 19 patients were referred to the Maxillofacial Surgery Department of San Paolo Hospital (Milan, Italy) with pain in the area supplied by the IAN, which developed following endodontic treatment, oral surgery and maxillofacial surgery. All patients underwent IAN surgery by several different microsurgical procedures. Most of the patients affected by pain before surgery experienced complete or partial amelioration of symptoms. All patients receiving sural nerve grafts were pain-free 12 months after surgery. In five patients the operation was unsuccessful. In 78.94% of cases, a significant increase in nerve function was observed. Pain following IAN surgical damage may be addressed by microsurgery; nerve substitution with a sural nerve interpositional graft appears to represent the most efficacious procedure. Scar releasing, nerve decompression and nerve substitution using vein grafts are less effective. Removal of endodontic material extravasated into the mandibular canal is mandatory and effective in patients experiencing severe pain. Surgery should be performed within 12 months postoperatively, ideally during the first few weeks after symptoms onset. PMID:26315275

  9. Spectral and Temporal Modulation Tradeoff in the Inferior Colliculus

    PubMed Central

    Rodríguez, Francisco A.; Read, Heather L.

    2010-01-01

    The cochlea encodes sounds through frequency-selective channels that exhibit low-pass modulation sensitivity. Unlike the cochlea, neurons in the auditory midbrain are tuned for spectral and temporal modulations found in natural sounds, yet the role of this transformation is not known. We report a distinct tradeoff in modulation sensitivity and tuning that is topographically ordered within the central nucleus of the inferior colliculus (CNIC). Spectrotemporal receptive fields (STRFs) were obtained with 16-channel electrodes inserted orthogonal to the isofrequency lamina. Surprisingly, temporal and spectral characteristics exhibited an opposing relationship along the tonotopic axis. For low best frequencies (BFs), units were selective for fast temporal and broad spectral modulations. A systematic progression was observed toward slower temporal and finer spectral modulation sensitivity at high BF. This tradeoff was strongly reflected in the arrangement of excitation and inhibition and, consequently, in the modulation tuning characteristics. Comparisons with auditory nerve fibers show that these trends oppose the pattern imposed by the peripheral filters. These results suggest that spectrotemporal preferences are reordered within the tonotopic axis of the CNIC. This topographic organization has profound implications for the coding of spectrotemporal features in natural sounds and could underlie a number of perceptual phenomena. PMID:20018831

  10. Serotonergic modulation of inhibitory synaptic transmission in mouse inferior colliculus.

    PubMed

    Obara, Nobuyuki; Kamiya, Haruyuki; Fukuda, Satoshi

    2014-01-01

    The inferior colliculus (IC) transmits the ascending auditory signal to the thalamic medial geniculate nucleus. Previous studies have reported that serotonergic input originating from the raphe nuclei has a strong influence on signal processing within the central nucleus of the IC. To identify the cellular target for the serotonergic modulation in the IC, we examined the effect of serotonin as well as selective serotonin reuptake inhibitor (SSRI) fluvoxamine on spontaneous GABAergic and glycinergic inhibitory postsynaptic currents (sIPSCs) recorded with whole-cell recordings.Consistent with earlier studies, we confirmed that serotonin robustly enhanced the frequency, but not amplitude, of GABAergic sIPSCs. It should be noted that the application of fluvoxamine alone marginally increased the frequency of GABAergic sIPSCs. These findings suggest that serotonin is endogenously released even in slice preparations, and it negatively modulates the tone of activity of inhibitory neurons within IC. We also examined the effect of serotonin and fluvoxamine on glycinergic sIPSCs and found that serotonin has a significantly weaker effect on glycinergic sIPSCs than on GABAergic sIPSCs. The differential sensitivity of the GABAergic and glycinergic sIPSCs to serotonin implies that serotonergic input plays a specific role in auditory information processing.Moreover, it suggests that the serotonergic input may contribute to pathological conditions such as tinnitus. PMID:24573204

  11. Left inferior parietal lobe engagement in social cognition and language.

    PubMed

    Bzdok, Danilo; Hartwigsen, Gesa; Reid, Andrew; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

    2016-09-01

    Social cognition and language are two core features of the human species. Despite distributed recruitment of brain regions in each mental capacity, the left parietal lobe (LPL) represents a zone of topographical convergence. The present study quantitatively summarizes hundreds of neuroimaging studies on social cognition and language. Using connectivity-based parcellation on a meta-analytically defined volume of interest (VOI), regional coactivation patterns within this VOI allowed identifying distinct subregions. Across parcellation solutions, two clusters emerged consistently in rostro-ventral and caudo-ventral aspects of the parietal VOI. Both clusters were functionally significantly associated with social-cognitive and language processing. In particular, the rostro-ventral cluster was associated with lower-level processing facets, while the caudo-ventral cluster was associated with higher-level processing facets in both mental capacities. Contrarily, in the (less stable) dorsal parietal VOI, all clusters reflected computation of general-purpose processes, such as working memory and matching tasks, that are frequently co-recruited by social or language processes. Our results hence favour a rostro-caudal distinction of lower- versus higher-level processes underlying social cognition and language in the left inferior parietal lobe. PMID:27241201

  12. Inferior vena cava filter placement in orthopedic surgery.

    PubMed

    Bass, Anne R; Mattern, Christopher J; Voos, James E; Peterson, Margaret G E; Trost, David W

    2010-09-01

    Inferior vena cava (IVC) filters were developed for the treatment of venous thromboembolism but in high-risk patients are often used for prophylaxis instead. In the study reported here, we reviewed all the orthopedic surgery cases in which IVC filters were used at our institution in 2005. Charts were analyzed and patients contacted by telephone for long-term follow-up. IVC filters were used in 90 (0.96%) of the 9,348 inpatient orthopedic surgeries. Sixty-one percent of filters were placed for prophylaxis, though only 42% of patients with prophylactic filters had a contraindication to anticoagulation. Eighty-one percent of patients with prophylactic filters who received anticoagulation received warfarin. Ratios of prophylactic-to-treatment filters were 3.25 for fracture surgeries, 2.1 for arthroplasties, and 0.89 for spine surgeries. Five percent of patients with prophylactic filters developed deep vein thrombosis. Fifty-two percent of filters were retrievable, but only 40% of those were removed a mean of 5.1 months (SD, 3.9 months) after placement. Filter removal was associated with complications in 11% of patients, and in another 10% the filter could not be removed. Forty-one patients were contacted a mean of 21 months (SD, 3 months) after filter placement. Only 32% of those who still had filters were on anticoagulation at follow-up. PMID:21290021

  13. Lagged cells in the inferior colliculus of the awake ferret

    PubMed Central

    Shechter, Barak; Marvit, Peter; Depireux, Didier A

    2010-01-01

    Neurons in primary auditory cortex (AI) encode complex features of the spectral content of sound, such as direction selectivity. Recent findings of temporal symmetry in AI predict a specific organization of the subcortical input into cortex that contributes to the emergence of direction selectivity. We demonstrate two sub-populations of neurons in the central nucleus of the inferior colliculus, which differ in their steady-state temporal response profile: lagged and non-lagged. The lagged cells (23%) are shifted in temporal phase with respect to non-lagged cells and are characterized by an “inhibition first” and delayed excitation in their spectro-temporal receptive fields. Non-lagged cells (77%) have a canonical “excitation first” response. However, we find no difference in the response onset latency to pure tone stimuli between the two sub-populations. Given the homogeneity of tonal response latency, we predict that these lagged cells receive inhibitory input mediated by cortical feedback projections. PMID:20092554

  14. Circulating miRNAs as Potential Marker for Pulmonary Hypertension

    PubMed Central

    Wei, Chuanyu; Henderson, Heather; Spradley, Christopher; Li, Li; Kim, Il-Kwon; Kumar, Sandeep; Hong, Nayeon; Arroliga, Alejandro C.; Gupta, Sudhiranjan

    2013-01-01

    MircoRNAs (miRNAs) are small non-coding RNAs that govern the gene expression and, play significant role in the pathogenesis of heart failure. The detection of miRNAs in circulation of pulmonary hypertensive (PH) human subjects remains elusive. In the current study, we determined the pattern of miRNAs of mild-to-severe human PH subjects and, compared them with the control subjects by miRNA array. Blood was obtained using fluoroscopic and waveform guided catheterization from the distal (pulmonary artery) port of the catheter. A total 40 human subjects were included in the study and, the degree of PH was determined by mean pulmonary arterial pressure. Among several miRNAs in the array, we validated 14 miRNAs and, the data were consistent with the array profile. We identified several novel downregulated miRNAs (miR-451, miR-1246) and upregulated miRNAs (miR-23b, miR-130a and miR-191) in the circulation of PH subjects. Our study showed novel set of miRNAs which are dysregulated in PH and, are directly proportional to the degree of PH. These miRNAs may be considered as potential biomarker for early detection of PH. PMID:23717609

  15. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

    PubMed Central

    Kilian, Yvonne; Wehmeier, Udo F.; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods:Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30′, 60′, 180′) and HVT (d3, 0′, 60′). Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues. PMID:27014090

  16. Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis.

    PubMed

    Linden, David R

    2012-11-01

    Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during "acute" inflammation. Hyperexcitability persisted at 6 days post-TNBS during "chronic" inflammation, as well as at 56 days post-TNBS when colitis had resolved. In contrast, there was only a modest decrease in the current required to elicit an action potential at 24 h after acetic acid administration. Vasomotor neurons from inflamed preparations exhibited normal excitability. The excitatory effects of XE-991, a blocker of the channel that contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of the channel that contributes to the A-type potassium current, were unchanged in TNBS-inflamed preparations, suggesting that these currents did not contribute to hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused tonic visceromotor neurons to accommodate to sustained current pulses, regardless of the inflammatory state of the preparation, and restored a normal rheobase in neurons from TNBS-inflamed preparations but did not alter the rheobase of control preparations, suggesting that enhanced activity of voltage-gated sodium channels may contribute to colitis-induced hyperexcitability. Collectively, these data indicate that enhanced sympathetic drive as a result of hyperexcitable visceromotor neurons may contribute to small bowel dysfunction during colitis. PMID:22961805

  17. Effect of current focusing on the sensitivity of inferior colliculus neurons to amplitude-modulated stimulation.

    PubMed

    George, Shefin S; Shivdasani, Mohit N; Fallon, James B

    2016-09-01

    In multichannel cochlear implants (CIs), current is delivered to specific electrodes along the cochlea in the form of amplitude-modulated pulse trains, to convey temporal and spectral cues. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation and reduced channel interactions in the inferior colliculus (IC) compared with traditional monopolar (MP) stimulation, suggesting that focusing of stimulation could produce better transmission of spectral information. The present study explored the capability of IC neurons to detect modulated CI stimulation with FMP and TP stimulation compared with MP stimulation. The study examined multiunit responses of IC neurons in acutely deafened guinea pigs by systematically varying the stimulation configuration, modulation depth, and stimulation level. Stimuli were sinusoidal amplitude-modulated pulse trains (carrier rate of 120 pulses/s). Modulation sensitivity was quantified by measuring modulation detection thresholds (MDTs), defined as the lowest modulation depth required to differentiate the response of a modulated stimulus from an unmodulated one. Whereas MP stimulation showed significantly lower MDTs than FMP and TP stimulation (P values <0.05) at stimulation ≤2 dB above threshold, all stimulation configurations were found to have similar modulation sensitivities at 4 dB above threshold. There was no difference found in modulation sensitivity between FMP and TP stimulation. The present study demonstrates that current focusing techniques such as FMP and TP can adequately convey amplitude modulation and are comparable to MP stimulation, especially at higher stimulation levels, although there may be some trade-off between spectral and temporal fidelity with current focusing stimulation. PMID:27306672

  18. Phlegmasia Caerulea Dolens in a Patient With an Inferior Vena Cava Filter: Treatment of Massive Iliocaval Thrombosis Using Local Intravenous Catheter-Directed Thrombolysis

    SciTech Connect

    Cookson, Daniel; Caldwell, Stuart

    2012-10-15

    Phlegmasia caerulea dolens (PCD) is a potentially disastrous complication of inferior vena cava filter insertion, and its optimum management has not been clearly established. We present a case report of a patient with pulmonary embolism and acute adrenal haemorrhage who developed PCD secondary to massive iliocaval thrombosis after insertion of a Cook Celect removable filter. Local intravenous catheter-directed thrombolysis (CDT), followed by systemic anticoagulation, achieved limb salvage and virtual resolution of symptoms at 3 months without complications. CDT can be a successful primary treatment of filter-associated PCD and can be safe in selected patients with acute nontraumatic haemorrhage. Systemic anticoagulation may subsequently restore complete venous patency and may therefore be a useful approach to postthrombolysis management of residual iliocaval thrombus when filter removal is indicated.

  19. Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line.

    PubMed

    Zhong, Hua; Wang, Hai-rong; Yang, Shuang; Zhong, Ji-hua; Wang, Ting; Wang, Chun; Chen, Fang-yuan

    2010-07-01

    The expression pattern of microRNAs (miRNAs) and their potential target genes were investigated in acute promyelocytic leukemia (APL) cell line NB4 cells during all-trans-retinoid acid (ATRA) treatment by using a miRNA microarrays platform and real-time quantitative PCR (RTQ-PCR). MiR-146a as one of the miRNAs down-regulated by ATRA during APL differentiation was identified. Direct interaction between miR146a and its predictive target gene Smad4 were confirmed by Luciferase assay. Down-regulation of miR-146a and upregulation of Smad4 at protein levels were demonstrated. These data suggested that miR-146a might influence proliferation of APL cells through TGF-beta1/Smad signal transduction pathway during ATRA induction. PMID:20577838

  20. Converging miRNA functions in diverse brain disorders: A case for miR-124 and miR-126

    PubMed Central

    Sonntag, Kai C.; Woo, Tsung-Ung W.; Krichevsky, Anna M.

    2012-01-01

    A growing body of information on the biology of miRNAs has revealed new insight into their roles in normal homeostasis and pathology of disease. miRNAs control all steps of the cellular expression machinery acting through a “single miRNA/multiple targets” or “multiple miRNAs/single target” mechanism. They have profound impact on the regulation of signaling pathways, which govern common and specific functions across different cellular phenotypes. There is increasing evidence that various diseases share similar disturbances in gene expression networks. Since miRNAs have both common and varying effects in different cellular contexts, they might also influence overlapping signaling pathways in different organs and disease entities. Here, we review this concept for two miRNAs highly abundant in the brain, miR-124 and miR-126, and their potential role in diseases of the brain. PMID:22178324

  1. miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene

    PubMed Central

    Fu, Qiang; Qin, Tao; Chen, Lin; Liu, Chuan-Jiang; Zhang, Xu; Wang, Yu-Zhu; Hu, Ming-Xing; Chu, Hao-Yuan; Zhang, Hong-Wei

    2016-01-01

    AIM: To investigate the expression of miR-29a in rat acute pancreatitis and its functional role in AR42J cell apoptosis. METHODS: Twelve SD rats were divided into a control group and an acute edematous pancreatitis (AEP) group randomly. AEP was induced by intraperitoneal injection of L-arginine (150 mg/kg) in the AEP group and equal volume of 0.9% NaCl was injected in the control group. The apoptosis of acinar cells in pancreatic tissue was determined by TUNEL assay. miRNA chip assay was performed to examine the expression of miRNAs in two groups. Besides, to further explore the role of miR-29a in apoptosis in vitro, recombinant rat TNF-α (50 ng/mL) was administered to treat the rat pancreatic acinar cell line AR42J for inducing AR42J cell apoptosis. Quantitative real-time PCR (qRT-PCR) was adopted to measure miR-29a expression. Then, miRNA mimic, miRNA antisense oligonucleotide (AMO) and control vector were used to transfect AR42J cells. The expression of miR-29a was confirmed by qRT-PCR and the apoptosis rate of AR42J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of activated caspase3. Moreover, we used bioinformatics software and luciferase assay to test whether TNFRSF1A was the target gene of miR-29a. After transfection, qRT-PCR and Western blot was used to detect the expression of TNFRSF1A in AR42J cells after transfection. RESULTS: The expression of miR-29a was much higher in the AEP group compared with the control group as displayed by the miRNA chip assay. After inducing apoptosis of AR42J cells in vitro, the expression of miR-29a was significantly increased by 1.49 ± 0.04 times in comparison with the control group. As revealed by qRT-PCR assay, the expression of miR-29a was 2.68 ± 0.56 times higher in the miR-29a mimic group relative to the control vector group, accompanied with an obviously increased acinar cell apoptosis rate (42.83 ± 1.25 vs 24.97 ± 0.15, P < 0.05). Moreover, the expression of miR-29a

  2. The functional role of microRNA in acute lymphoblastic leukemia: relevance for diagnosis, differential diagnosis, prognosis, and therapy

    PubMed Central

    Luan, Chengxin; Yang, Zixue; Chen, Baoan

    2015-01-01

    MicroRNAs (miRNAs), a new class of noncoding RNAs, which can hybridize to target messenger RNAs and regulate their expression posttranscriptionally, express differentially in distinct stages of lymphopoiesis and influence the direction of lymphoid precursor maturation. Hence, there is aberrant expression of miRNAs involved in malignant lymphopoiesis, and these aberrations can be used as signatures of acute lymphoblastic leukemia (ALL) with different subtypes. In addition, changes in the expression of several miRNAs may have functional relevance with leukemogenesis or drug resistance. As a result, the reversal of the expression of these miRNAs may alleviate the disease to some extent and improve clinical outcomes. However, among the studies of miRNAs, there are still some problems that need to be solved to understand the function of miRNAs in ALL more thoroughly. PMID:26508875

  3. Stress-related alcohol consumption in heavy drinkers correlates with expression of miR-10a, miR-21 and components of the TAR-RNA binding protein (TRBP)-associated complex

    PubMed Central

    Beech, Robert D.; Leffert, Janine J.; Lin, Aiping; Hong, Kwangik A.; Hansen, Julie; Umlauf, Sheila; Mane, Shrikant; Zhao, Hongyu; Sinha, Rajita

    2014-01-01

    their target genes is regulated by acute psychological stress, and is correlated with stress-induced drinking in a laboratory setting. Alterations in miRNA expression may be one mechanism linking psychological stress with changes in gene-expression and increased alcohol intake in binge/heavy drinkers. PMID:25421511

  4. Acute myelogenous leukemia (AML) - children

    MedlinePlus

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  5. CCAR1 5′ UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance

    PubMed Central

    Li, Gaopeng; Wu, Xiaoli; Qian, Wenchang; Cai, Huayong; Sun, Xinbao; Zhang, Weijie; Tan, Sheng; Wu, Zhengsheng; Qian, Pengxu; Ding, Keshuo; Lu, Xuefei; Zhang, Xiao; Yan, Hong; Song, Haifeng; Guang, Shouhong; Wu, Qingfa; Lobie, Peter E; Shan, Ge; Zhu, Tao

    2016-01-01

    MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5′ untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed “miRancers”, can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5′ UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization. PMID:27002217

  6. CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance.

    PubMed

    Li, Gaopeng; Wu, Xiaoli; Qian, Wenchang; Cai, Huayong; Sun, Xinbao; Zhang, Weijie; Tan, Sheng; Wu, Zhengsheng; Qian, Pengxu; Ding, Keshuo; Lu, Xuefei; Zhang, Xiao; Yan, Hong; Song, Haifeng; Guang, Shouhong; Wu, Qingfa; Lobie, Peter E; Shan, Ge; Zhu, Tao

    2016-06-01

    MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5' untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed "miRancers", can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5' UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization. PMID:27002217

  7. The Type I IFN-Induced miRNA, miR-21

    PubMed Central

    Yang, Chuan He; Li, Kui; Pfeffer, Susan R.; Pfeffer, Lawrence M.

    2015-01-01

    The interferon (IFN) family of cytokines not only has antiviral properties at various steps in the viral replication cycle, but also anticancer activity through multiple pathways that include inhibiting cell proliferation, regulating cellular responses to inducers of apoptosis and modulating angiogenesis and the immune system. IFNs are known to induce their biological activity through the induction of protein encoding IFN-stimulated genes. However, recent studies have established that IFNs also induce the expression of microRNAs (miRNAs), which are small endogenous non-coding RNAs that suppress gene expression at the post-transcriptional level. MiRNAs play critical roles in tumorigenesis and have been implicated to act as either oncogenes or tumor suppressors in various human cancers. Therefore, IFN-induced miRNAs play an important role, not only in the host response to innate immune response to cancer, but also in the tumorigenic process itself. Furthermore, IFN-induced miRNAs may participate in and/or orchestrate antiviral defense in certain viral infections. In this review, we describe our recent studies on the induction of miR-21 by type I IFN, the role of the STAT3 and NFκB signaling pathways in IFN-induced miR-21 expression, the role of miR-21 in different cancers and the role of miR-21 in regulating the antiviral response. PMID:26610525

  8. Close correlation between magnetic properties and the soft phonon mode of the structural transition in <mi>BaFe>2<mi>As>2 and <mi>SrFe>2<mi>As>2

    SciTech Connect

    Parshall, D.; Pintschovius, L.; Niedziela, Jennifer L.; Castellan, J. -P.; Lamago, D.; Mittal, R.; Wolf, Th.; Reznik, Dmitry

    2015-04-27

    Parent compounds of Fe-based superconductors undergo a structural phase transition from a tetragonal to an orthorhombic structure. We investigated the temperature dependence of the frequencies of TA phonons that extrapolate to the shear vibrational mode at the zone center, which corresponds to the orthorhombic deformation of the crystal structure at low temperatures in <mi>BaFe>2<mi>As>2 and <mi>SrFe>2<mi>As>2. We found that acoustic phonons at small wave vectors soften gradually towards the transition from high temperatures, tracking the increase of the size of slowly fluctuating magnetic domains. On cooling below the transition to base temperature the phonons harden, following the square of the magnetic moment (which we find is proportional to the anisotropy gap). Finally, our results provide evidence for close correlation between magnetic and phonon properties in Fe-based superconductors.

  9. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance.

    PubMed

    Danza, Katia; Silvestris, Nicola; Simone, Giovanni; Signorile, Michele; Saragoni, Luca; Brunetti, Oronzo; Monti, Manlio; Mazzotta, Annalisa; De Summa, Simona; Mangia, Anita; Tommasi, Stefania

    2016-04-01

    Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy. PMID:26793992

  10. A genome-wide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomas

    PubMed Central

    Ng, Kimberly; Steed, Tyler; Nguyen, Thien; Futalan, Diahnn; Akers, Johnny C.; Sarkaria, Jann; Jiang, Tao; Chowdhury, Dipanjan; Carter, Bob S.; Chen, Clark C.

    2014-01-01

    MGMT expression is a critical determinant for therapeutic resistance to DNA alkylating agents. We previously demonstrated that MGMT expression is post-transcriptionally regulated by miR-181d and other miRNAs. Here, we performed a genome-wide screen to identify MGMT regulating miRNAs. Candidate miRNAs were further tested for inverse correlation with MGMT expression in clinical specimens. We identified 15 candidate miRNAs and characterized the top candidate, miR-603. Transfection of miR-603 suppressed MGMT mRNA/protein expression in vitro and in vivo; this effect was reversed by transfection with antimiR-603. miR-603 affinity-precipitated with MGMT mRNA and suppressed luciferase activity in an MGMT-3'UTR-luciferase assay, suggesting direct interaction between miR-603 and MGMT 3'UTR. miR-603 transfection enhanced the temozolomide (TMZ) sensitivity of MGMT-expressing glioblastoma cell lines. Importantly, miR-603 mediated MGMT suppression and TMZ resistance were reversed by expression of an MGMT cDNA. In a collection of 74 clinical glioblastoma specimens, both miR-603 and miR-181d levels inversely correlated with MGMT expression. Moreover, a combined index of the two miRNAs better reflected MGMT expression than each individually. These results suggest that MGMT is co-regulated by independent miRNAs. Characterization of these miRNAs should contribute toward strategies for enhancing the efficacy of DNA alkylating agents. PMID:24994119

  11. MicroRNAs in acute kidney injury.

    PubMed

    Fan, Pei-Chun; Chen, Chia-Chun; Chen, Yung-Chang; Chang, Yu-Sun; Chu, Pao-Hsien

    2016-01-01

    Acute kidney injury (AKI) is an important clinical issue that is associated with significant morbidity and mortality. Despite research advances over the past decades, the complex pathophysiology of AKI is not fully understood. The regulatory mechanisms underlying post-AKI repair and fibrosis have not been clarified either. Furthermore, there is no definitively effective treatment for AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23 nucleotides that have been shown to be crucial to the post-transcriptional regulation of various cellular biological functions, including proliferation, differentiation, metabolism, and apoptosis. In addition to being fundamental to normal development and physiology, miRNAs also play important roles in various human diseases. In AKI, some miRNAs appear to act pathogenically by promoting inflammation, apoptosis, and fibrosis, while others may act protectively by exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenic effects. Thus, miRNAs have not only emerged as novel biomarkers for AKI; they also hold promise to be potential therapeutic targets. PMID:27608623

  12. Introns of plant pri-miRNAs enhance miRNA biogenesis

    PubMed Central

    Bielewicz, Dawid; Kalak, Malgorzata; Kalyna, Maria; Windels, David; Barta, Andrea; Vazquez, Franck; Szweykowska-Kulinska, Zofia; Jarmolowski, Artur

    2013-01-01

    Plant MIR genes are independent transcription units that encode long primary miRNA precursors, which usually contain introns. For two miRNA genes, MIR163 and MIR161, we show that introns are crucial for the accumulation of proper levels of mature miRNA. Removal of the intron in both cases led to a drop-off in the level of mature miRNAs. We demonstrate that the stimulating effects of the intron mostly reside in the 5′ss rather than on a genuine splicing event. Our findings are biologically significant as the presence of functional splice sites in the MIR163 gene appears mandatory for pathogen-triggered accumulation of miR163 and proper regulation of at least one of its targets. PMID:23681439

  13. miR-99a/100∼125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling

    PubMed Central

    Emmrich, Stephan; Rasche, Mareike; Schöning, Jennifer; Reimer, Christina; Keihani, Sarva; Maroz, Aliaksandra; Xie, Ying; Li, Zhe; Schambach, Axel; Reinhardt, Dirk; Klusmann, Jan-Henning

    2014-01-01

    Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100∼125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor β (TGFβ) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active β-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFβ signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100∼125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL. PMID:24736844

  14. Identification of urinary microRNA biomarkers for detection of gentamicin-induced acute kidney injury in rats.

    PubMed

    Zhou, Xiaobing; Qu, Zhe; Zhu, Cong; Lin, Zhi; Huo, Yan; Wang, Xue; Wang, Jufeng; Li, Bo

    2016-07-01

    MicroRNAs (miRNAs) have been recently recognized as promising non-invasive biomarkers for detecting the organ injuries. To further understand the sensibility and reliability of miRNA measurements in urine sample for predicting drug-induced early nephrotoxicity, a global urinary miRNA expression analysis was performed in the rodent models with gentamicin-induced acute kidney injury (AKI). Male Wistar rats were daily administrated with gentamicin (0, 60, and 120 mg/kg) for up to 10 days by intraperitoneal injection, and the miRNA profiling of animal urine samples were subsequently analyzed using TaqMan(®) Array Rodent miRNA Cards. The results showed that four miRNAs (mmu-miR-138-5p, mmu-miR-1971, mmu-miR-218-1-3p, and rno-miR-489) were continuously increased in urine samples since day 4 after administration with gentamicin, which was not reflected by the standard markers such as serum creatinine (Cr) and urea nitrogen (BUN). Furthermore, other nine urinary miRNAs were increased in both 60 and 120 mg/kg groups on day 8. Receiver operator characteristics analysis demonstrated that the performance of these miRNAs with time- or dose-dependent increases were comparable to standard biomarkers (i.e. serum Cr and BUN), suggesting that the urinary miRNA panel can be used as potential biomarkers for the detection of gentamicin-induced AKI in rats. Moreover, the computer prediction analysis showed that these differentially expressed miRNAs were potentially targeted to many genes, which were mainly associated with the regulation of metabolic process and signaling. These data will improve the understanding and prediction of toxicology processes induced by nephrotoxicants. PMID:27074385

  15. Discovery of miRNAs and Their Corresponding miRNA Genes in Atlantic Cod (Gadus morhua): Use of Stable miRNAs as Reference Genes Reveals Subgroups of miRNAs That Are Highly Expressed in Particular Organs

    PubMed Central

    Andreassen, Rune; Rangnes, Fredrik; Sivertsen, Maria; Chiang, Michelle; Tran, Michelle; Worren, Merete Molton

    2016-01-01

    Background Atlantic cod (Gadus morhua) is among the economically most important species in the northern Atlantic Ocean and a model species for studying development of the immune system in vertebrates. MicroRNAs (miRNAs) are an abundant class of small RNA molecules that regulate fundamental biological processes at the post-transcriptional level. Detailed knowledge about a species miRNA repertoire is necessary to study how the miRNA transcriptome modulate gene expression. We have therefore discovered and characterized mature miRNAs and their corresponding miRNA genes in Atlantic cod. We have also performed a validation study to identify suitable reference genes for RT-qPCR analysis of miRNA expression in Atlantic cod. Finally, we utilized the newly characterized miRNA repertoire and the dedicated RT-qPCR method to reveal miRNAs that are highly expressed in certain organs. Results The discovery analysis revealed 490 mature miRNAs (401 unique sequences) along with precursor sequences and genomic location of the miRNA genes. Twenty six of these were novel miRNA genes. Validation studies ranked gmo-miR-17-1—5p or the two-gene combination gmo-miR25-3p and gmo-miR210-5p as most suitable qPCR reference genes. Analysis by RT-qPCR revealed 45 miRNAs with significantly higher expression in tissues from one or a few organs. Comparisons to other vertebrates indicate that some of these miRNAs may regulate processes like growth, lipid metabolism, immune response to microbial infections and scar damage repair. Three teleost-specific and three novel Atlantic cod miRNAs were among the differentially expressed miRNAs. Conclusions The number of known mature miRNAs was considerably increased by our identification of miRNAs and miRNA genes in Atlantic cod. This will benefit further functional studies of miRNA expression using deep sequencing methods. The validation study showed that stable miRNAs are suitable reference genes for RT-qPCR analysis of miRNA expression. Applying RT-qPCR we

  16. Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.; Ufferman, R. C.

    1971-01-01

    Study of the differential characteristics of hepatic congestion and decreased cardiac output in terms of potential afferent stimuli in the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction. An attempt is made to see if the autonomic nervous system is involved in the antinatriuretic effect of acute TIVC or thoracic superior vena cava constriction.

  17. Determinants of survival after inferior vena cava trauma.

    PubMed

    Kuehne, J; Frankhouse, J; Modrall, G; Golshani, S; Aziz, I; Demetriades, D; Yellin, A E

    1999-10-01

    Inferior vena cava (IVC) injuries continue to be associated with mortality rates of 21 to 66 per cent despite advances in prehospital, surgical, and critical care. The purpose of this study was to evaluate outcome of patients with IVC injury after treatment at a major urban trauma center and to identify factors predictive of survival. Between 1989 and 1995, 158 patients presented to the Los Angeles County + University of Southern California Medical Center with IVC injuries. One hundred thirty-six patient records were available for review, and 69 data points were collected and analyzed. Mean age was 26 years (range, 6-54), and 122 (90%) patients were male. Mechanism of injury included gunshot in 88 (65%) patients, stab in 23 (17%) patients, shotgun in 7 (5%) patients, and blunt trauma in 18 (13%) patients. The mean Injury Severity Score was 25. Seventy (52%) patients were hypotensive. Eleven (8%) patients died before surgical intervention, and 25 (18%) patients died before operative repair. Repair (79), ligation (20), or observation (1) was accomplished in 100 (74%) patients. Overall survival was 48 per cent and 65 per cent in the 100 patients surviving to operative repair, including 5 of 20 patients requiring IVC ligation. Significant differences (P<0.001) between survivors and nonsurvivors included Injury Severity Score, Glasgow Coma Score, hematocrit, hypotension, emergent thoracotomy, blood loss, level of injury, tamponade, and associated aortic injury. Logistic regression analysis identified hypotension, anatomic level of injury, and associated aortic injury as significant predictors of outcome (P = 0.001). Survival is predominantly determined by severity and anatomic accessibility of the IVC injury and by the absence of associated major vascular injuries. Ligation may control otherwise exsanguinating injuries and should be considered early in the management of complex injuries. PMID:10515547

  18. Radiofrequency volumetric inferior turbinate reduction: long-term clinical results.

    PubMed

    De Corso, E; Bastanza, G; Di Donfrancesco, V; Guidi, M L; Morelli Sbarra, G; Passali, G C; Poscia, A; de Waure, C; Paludetti, G; Galli, J

    2016-06-01

    The aim of our study was to assess long-term results of radiofrequency volumetric tissue reduction of inferior turbinates (RVTR). We performed a prospective long-term longitudinal evaluation of 305 patients affected by rhinitis (114 allergic and 191 non-allergic) who were unresponsive to medical treatment and underwent RVTR (January 2004 - December 2010). Subjects were followed for a mean period of 39.70 ± 19.41 months (range 24-60). Patients completed the NOSE-scale questionnaire pre- and post-operatively after 1 month and yearly for 5-years. Recurrence was assumed if the post-operative total NOSE score increased by at least 75% during follow-up and the patient restarted medical treatments. Estimation of relapse over time was performed by Kaplan-Meyer analyses. We documented overall good satisfaction of patients regarding the procedure, with a good rate of pain control and a low rate of complications. Post-operatively there was a significant improvement in nasal stuffiness, nasal obstruction and mouth breathing (p < 0.05). We observed a worsening trend for symptoms after 36 months with progressive increasing rate of recurrences that were significantly higher in allergic than non-allergic patients (p < 0.05). We also observed a slight worsening trend of global satisfaction of patients. Our study confirms the minor discomfort and low risk of side effects of RVTR. Our data showed good efficacy of the procedure in the majority of patients for at least 36 months after surgery, and in fact in this time period the cumulative probability to remain relapse-free was up to 0.8. In the following 2 years, we observed a worse temporal trend in term of recurrence rate, and in particular in allergic patients with a significant difference vs non-allergic individuals (p < 0.05). PMID:27214831

  19. Sources of adaptation of inferior temporal cortical responses.

    PubMed

    Vogels, Rufin

    2016-07-01

    Neurons of different brain regions change their response when a stimulus is repeated. In inferior temporal cortex (IT), stimulus repetition typically reduces the responses of single neurons, i.e., IT neurons show repetition suppression. Single unit recordings in IT showed that individual neurons vary in their degree of adaptation effects, ranging from strong suppression to slight enhancement of the response to the repeated stimulus. The suppression is maximal after the peak of the response and then reduces during the further course of the response. Repetition suppression in IT is still present for interstimulus intervals of at least 900 msec. I discuss the contribution of mechanisms that have been proposed to explain adaptation effects of IT responses. Firing-rate dependent response fatigue, e.g., a prolonged hyperpolarization, intrinsic to the recorded neuron cannot explain the stimulus specificity of the adaptation effect. The latter can be explained by synaptic depression or an adapted input from other IT neurons. We observed repetition suppression of IT neurons when adapter and test stimuli were presented at locations that differed by 8 degree of visual angle, suggesting that at least part of the adaptation effect is not inherited from retinotopic visual areas with small receptive fields. We observed no effect of repetition probability on repetition suppression in macaque IT using images of various categories, suggesting a dissociation between top-down expectation effects and repetition suppression. Together, our data agree with the hypothesis that adaptation in IT serves to reduce the saliency of recently seen stimuli, highlighting stimuli that differ from recently presented ones. PMID:26518166

  20. Bifurcation of orbits and synchrony in inferior olive neurons.

    PubMed

    Lee, Keum W; Singh, Sahjendra N

    2012-09-01

    Inferior olive neurons (IONs) have rich dynamics and can exhibit stable, unstable, periodic, and even chaotic trajectories. This paper presents an analysis of bifurcation of periodic orbits of an ION when its two key parameters (a, μ) are varied in a two-dimensional plane. The parameter a describes the shape of the parabolic nonlinearity in the model and μ is the extracellular stimulus. The four-dimensional ION model considered here is a cascade connection of two subsystems (S(a) and S(b)). The parameter plane (a - μ) is delineated into several subregions. The ION has distinct orbit structure and stability property in each subregion. It is shown that the subsystem S(a) or S(b) undergoes supercritical Poincare-Andronov-Hopf (PAH) bifurcation at a critical value μ(c)(a) of the extracellular stimulus and periodic orbits of the neuron are born. Based on the center manifold theory, the existence of periodic orbits in the asymptotically stable S(a), when the subsystem S(b) undergoes PAH bifurcation, is established. In such a case, both subsystems exhibit periodic orbits. Interestingly when S(b) is under PAH bifurcation and S(a) is unstable, the trajectory of S(a) exhibits periodic bursting, interrupted by periods of quiescence. The bifurcation analysis is followed by the design of (i) a linear first-order filter and (ii) a nonlinear control system for the synchronization of IONs. The first controller uses a single output of each ION, but the nonlinear control system uses two state variables for feedback. The open-loop and closed-loop responses are presented which show bifurcation of orbits and synchronization of oscillating neurons. PMID:21898110

  1. Retrievable Inferior Vena Cava Filters: Factors that Affect Retrieval Success

    SciTech Connect

    Geisbuesch, Philipp Benenati, James F.; Pena, Constantino S.; Couvillon, Joseph; Powell, Alex; Gandhi, Ripal; Samuels, Shaun; Uthoff, Heiko

    2012-10-15

    Purpose: To report and analyze the indications, procedural success, and complications of retrievable inferior vena cava filters (rIVCF) placement and to identify parameters that influence retrieval attempt and failure. Methods: Between January 2005 and December 2010, a total of 200 patients (80 men, median age 67 years, range 11-95 years) received a rIVCF with the clinical possibility that it could be removed. All patients with rIVCF were prospectively entered into a database and followed until retrieval or a decision not to retrieve the filter was made. A retrospective analysis of this database was performed. Results: Sixty-one percent of patients had an accepted indication for filter placement; 39% of patients had a relative indication. There was a tendency toward a higher retrieval rate in patients with relative indications (40% vs. 55%, P = 0.076). Filter placement was technically successful in all patients, with no procedure-related mortality. The retrieval rate was 53%. Patient age of >80 years (odds ratio [OR] 0.056, P > 0.0001) and presence of malignancy (OR 0.303, P = 0.003) was associated with a significantly reduced probability for attempted retrieval. Retrieval failure occurred in 7% (6 of 91) of all retrieval attempts. A time interval of > 90 days between implantation and attempted retrieval was associated with retrieval failure (OR 19.8, P = 0.009). Conclusions: Patient age >80 years and a history of malignancy are predictors of a reduced probability for retrieval attempt. The rate of retrieval failure is low and seems to be associated with a time interval of >90 days between filter placement and retrieval.

  2. Venous Thromboembolism After Removal of Retrievable Inferior Vena Cava Filters

    SciTech Connect

    Yamagami, Takuji Tanaka, Osamu; Yoshimatsu, Rika; Miura, Hiroshi; Nishimura, Tsunehiko

    2010-02-15

    The purpose of this study was to examine the incidence of new or recurrent venous thromboembolism (VTE) after retrieval of inferior vena cava (IVC) filters and risk factors associated with such recurrence. Between March 2001 and September 2008, at our institution, implanted retrievable vena cava filters were retrieved in 76 patients. The incidence of new or recurrent VTE after retrieval was reviewed and numerous variables were analyzed to assess risk factors for redevelopment of VTE after filter retrieval. In 5 (6.6%) of the 76 patients, redevelopment or worsening of VTE was seen after retrieval of the filter. Three patients (4.0%) had recurrent deep venous thrombosis (DVT) in the lower extremities and 2 (2.6%) had development of pulmonary embolism, resulting in death. Although there was no significant difference in the incidence of new or recurrent VTE related to any risk factor investigated, a tendency for development of VTE after filter retrieval was higher in patients in whom DVT in the lower extremities had been so severe during filter implantation that interventional radiological therapies in addition to traditional anticoagulation therapies were required (40% in patients with recurrent VTE vs. 23% in those without VTE; p = 0.5866 according to Fisher's exact probability test) and in patients in whom DVT remained at the time of filter retrieval (60% in patients with recurrent VTE vs. 37% in those without VTE; p = 0.3637). In conclusion, new or recurrent VTE was rare after retrieval of IVC filters but was most likely to occur in patients who had severe DVT during filter implantation and/or in patients with a DVT that remained at the time of filter retrieval. We must point out that the fatality rate from PE after filter removal was high (2.6%).

  3. Temporary Inferior Vena Cava Filters: How Do We Move Forward?

    PubMed

    Arous, Edward J; Messina, Louis M

    2016-05-01

    Despite their widespread use, the indications for the selective use of temporary inferior vena cava (IVC) filters remains uncertain with few trials supporting their use. Additionally, the risks of long-term temporary IVC filter insertion are being increasingly discussed amongst the mainstream media and through multiple class action lawsuits. Retrievable IVC filters were specifically designed to have a less secure implantation in order to facilitate retrieval. However, multiple reports have demonstrated significant filter-related complications, most commonly related to duration of implantation. Furthermore, the risk is not isolated to one manufacturer alone. The incidence of filter-related complications is linearly related to its duration of time on the market. Currently, the FDA recommends that IVC filters be removed within 25-54 days of their implantation. Unfortunately, little evidence exists to show that this recommendation is followed routinely. Recently, the PRESERVE Trial (NCT02381509) was initiated as a multicenter non-randomized open label study to determine the safety and effectiveness of commercially available IVC filters (both temporary and permanent) in individuals who require mechanical prophylaxis against pulmonary embolism. Until such evidence is developed, temporary IVC filters should be implanted based on best available evidence and routinely removed within the guidelines of the FDA of 25-54 days. A fair question at this point is whether the design features themselves that are required to manufacture a low profile removable IVC filter can achieve effective prophylaxis against pulmonary embolism at a low rate of short and long-term complications. PMID:27012891

  4. "Mini-Flow-Through" Deep Inferior Epigastric Perforator Flap for Breast Reconstruction with Preservation of Both Internal Mammary and Deep Inferior Epigastric Vessels

    PubMed Central

    Sugawara, Jun; Yasumura, Kazunori; Mikami, Taro; Kobayashi, Shinji; Maegawa, Jiro

    2015-01-01

    This procedure was developed for preservation of the rectus muscle components and deep inferior epigastric vessel after deep inferior epigastric perforator (DIEP) flap harvesting. A 53-year-old woman with granuloma caused by silicone injection underwent bilateral nipple-sparing mastectomies and immediate reconstruction with "mini-flow-through" DIEP flaps. The flaps were dissected based on the single largest perforator with a short segment of the lateral branch of the deep inferior epigastric vessel that was transected as a free flap for breast reconstruction. The short segments of the donor deep inferior epigastric vessel branch are primarily end-to-end anastomosed to each other. A short T-shaped pedicle mini-flow-through DIEP flap is interposed in the incised recipient's internal mammary vessels with two arterial and four concomitant venous anastomoses. Although it requires multiple vascular anastomoses and a short pedicle for the flap setting, the mini-flow-through DIEP flap provides a large pedicle caliber, enabling safer microsurgical anastomosis and well-vascularized tissue for creating a natural breast without consuming time or compromising the rectus muscle components and vascular flow of both the deep inferior epigastric and internal mammary vessels. PMID:26618128

  5. Polysome shift assay for direct measurement of miRNA inhibition by anti-miRNA drugs.

    PubMed

    Androsavich, John R; Sobczynski, Daniel J; Liu, Xueqing; Pandya, Shweta; Kaimal, Vivek; Owen, Tate; Liu, Kai; MacKenna, Deidre A; Chau, B Nelson

    2016-01-29

    Anti-miRNA (anti-miR) oligonucleotide drugs are being developed to inhibit overactive miRNAs linked to disease. To help facilitate the transition from concept to clinic, new research tools are required. Here we report a novel method--miRNA Polysome Shift Assay (miPSA)--for direct measurement of miRNA engagement by anti-miR, which is more robust than conventional pharmacodynamics using downstream target gene derepression. The method takes advantage of size differences between active and inhibited miRNA complexes. Active miRNAs bind target mRNAs in high molecular weight polysome complexes, while inhibited miRNAs are sterically blocked by anti-miRs from forming this interaction. These two states can be assessed by fractionating tissue or cell lysates using differential ultracentrifugation through sucrose gradients. Accordingly, anti-miR treatment causes a specific shift of cognate miRNA from heavy to light density fractions. The magnitude of this shift is dose-responsive and maintains a linear relationship with downstream target gene derepression while providing a substantially higher dynamic window for aiding drug discovery. In contrast, we found that the commonly used 'RT-interference' approach, which assumes that inhibited miRNA is undetectable by RT-qPCR, can yield unreliable results that poorly reflect the binding stoichiometry of anti-miR to miRNA. We also demonstrate that the miPSA has additional utility in assessing anti-miR cross-reactivity with miRNAs sharing similar seed sequences. PMID:26384419

  6. Polysome shift assay for direct measurement of miRNA inhibition by anti-miRNA drugs

    PubMed Central

    Androsavich, John R.; Sobczynski, Daniel J.; Liu, Xueqing; Pandya, Shweta; Kaimal, Vivek; Owen, Tate; Liu, Kai; MacKenna, Deidre A.; Chau, B. Nelson

    2016-01-01

    Anti-miRNA (anti-miR) oligonucleotide drugs are being developed to inhibit overactive miRNAs linked to disease. To help facilitate the transition from concept to clinic, new research tools are required. Here we report a novel method—miRNA Polysome Shift Assay (miPSA)—for direct measurement of miRNA engagement by anti-miR, which is more robust than conventional pharmacodynamics using downstream target gene derepression. The method takes advantage of size differences between active and inhibited miRNA complexes. Active miRNAs bind target mRNAs in high molecular weight polysome complexes, while inhibited miRNAs are sterically blocked by anti-miRs from forming this interaction. These two states can be assessed by fractionating tissue or cell lysates using differential ultracentrifugation through sucrose gradients. Accordingly, anti-miR treatment causes a specific shift of cognate miRNA from heavy to light density fractions. The magnitude of this shift is dose-responsive and maintains a linear relationship with downstream target gene derepression while providing a substantially higher dynamic window for aiding drug discovery. In contrast, we found that the commonly used ‘RT-interference’ approach, which assumes that inhibited miRNA is undetectable by RT-qPCR, can yield unreliable results that poorly reflect the binding stoichiometry of anti-miR to miRNA. We also demonstrate that the miPSA has additional utility in assessing anti-miR cross-reactivity with miRNAs sharing similar seed sequences. PMID:26384419

  7. miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia

    PubMed Central

    Navarro, A; Pairet, S; Álvarez-Larrán, A; Pons, A; Ferrer, G; Longarón, R; Fernández-Rodríguez, C; Camacho, L; Monzó, M; Besses, C; Bellosillo, B

    2016-01-01

    The biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature (P<0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a (P=0.045), miR-150 (P=0.001) and miR-519a (P=0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3. PMID:26990535

  8. miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer

    PubMed Central

    Letelier, Pablo; García, Patricia; Leal, Pamela; Álvarez, Héctor; Ili, Carmen; López, Jaime; Castillo, Jonathan; Brebi, Priscilla; Roa, Juan Carlos

    2014-01-01

    The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value < 0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P < 0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC. PMID:24966896

  9. MI Gap Clearing Kicker Magnet Design Review

    SciTech Connect

    Jensen, Chris; /Fermilab

    2008-10-01

    The kicker system requirements were originally conceived for the NOvA project. NOvA is a neutrino experiment located in Minnesota. To achieve the desired neutrino flux several upgrades are required to the accelerator complex. The Recycler will be used as a proton pre-injector for the Main Injector (MI). As the Recycler is the same size as the MI, it is possible to do a single turn fill ({approx}11 {micro}sec), minimizing the proton injection time in the MI cycle and maximizing the protons on target. The Recycler can then be filled with beam while the MI is ramping to extract beam to the target. To do this requires two new transfer lines. The existing Recycler injection line was designed for 10{pi} pbar beams, not the 20{pi} proton beams we anticipate from the Booster. The existing Recycler extraction line allows for proton injection through the MI, while we want direct injection from the Booster. These two lines will be decommissioned. The new injection line from the MI8 line into the Recycler will start at 848 and end with injection kickers at RR104. The new extraction line in the RR30 straight section will start with a new extraction kicker at RR232 and end with new MI injection kickers at MI308. Finally, to reduce beam loss activation in the enclosure, a new gap clearing kicker will be used to extract uncaptured beam created during the slip stack injection process down the existing dump line. It was suggested that the MI could benefit from this type of system immediately. This led to the early installation of the gap clearing system in the MI, followed by moving the system to Recycler during NOvA. The specifications also changed during this process. Initially the rise and fall time requirements were 38 ns and the field stability was {+-}1%. The 38 ns is based on having a gap of 2 RF buckets between injections. (There are 84 RF buckets that can be filled from the Booster for each injection, but 82 would be filled with beam. MI and Recycler contain 588 RF buckets

  10. Clinical, Histopathological and Therapeutical Analysis of Inferior Eyelid Basal Cell Carcinomas

    PubMed Central

    Totir, M; Alexandrescu, C; Pirvulescu, R; Gradinaru, S; Costache, M

    2014-01-01

    Rationale: Eyelids are very susceptible area for non-melanoma skin cancers; among that, basal cell carcinoma has the highest incidence (almost 90% of malignant eyelid tumors) and 50-60% of eyelid basal cell carcinomas appear on inferior eyelid. Objective: To analyze clinical features of inferior eyelid basal cell carcinoma and to determine the efficacy of surgical treatment with frozen sectioncontrolled margins and methods of primary reconstruction of defects. Methods: A review of medical records of cases with primary inferior eyelid basal cell carcinoma treated by surgical excision with urgent histopathology controlled margins by FS technique, doubled by paraffin examination from October 2011 to October 2014. After histopathology confirmation of tumor free margins, proper inferior eyelid reconstruction was performed. Results: The review resulted in 36 patients with 36 lesions analyzed by clinical, histopatological and therapeuticalaspectswith a mean follow-up of 20 months. All lesions were primary BCC affecting inferior eyelid. There were no recurrence in the follow-up period. Inferior eyelid reconstruction techniques were direct closure for small defects and complex techniques for defects more than one third of eyelid length. Discussion: Appropriate eyelid examination is mandatory in any routine ophthalmic check-up. Clinical signs suggestive of BCC should be familiar to ophthalmologist in order to have an early diagnosis and treatment for these tumors. Surgical treatment with FS controlled excision followed by eyelid reconstruction is an efficient treatment for inferior eyelid BCC. Abbreviations: basal cell carcinoma (BCC); frozen section (FS);Mohs micrographic surgery (MMS). PMID:27057245

  11. tRFs: miRNAs in disguise.

    PubMed

    Venkatesh, Thejaswini; Suresh, Padmanaban S; Tsutsumi, Rie

    2016-04-01

    tRFs and tiRNAs are two new classes of regulatory non-coding small RNAs that are derived from the cleavage of pre-existing tRNAs. tRFs are 18-22 nt long and are classified into the tRF-5, tRF-3, and tRF-1 series. Here, we discuss in detail the regulatory roles of tRFs in translation, viral infections, and carcinogenesis. Moreover, we have reviewed the association of tRFs with Argonaute proteins, including their potential to function as miRNAs. Interestingly, few miRNAs are generated from pre-existing tRNAs. Hence, tRNAs generate similar-sized tRFs and miRNAs, leading to misannotations due to cross mapping of tRFs and tRNA-derived miRNAs during deep sequencing data analysis. Therefore, it is important to catalogue the overlapping sequences between tRNA-derived miRNAs and tRFs. We have catalogued the miRNAs that overlap with tRFs sequences in humans using miRBase. We identified 20 tRNA-derived miRNAs that share sequences with tRFs. Of the 20 miRNAs, 5 miRNAs (miR-3182, miR-4521, miR-1260a, miR-1260b, and miR-7977) showed significant prediction scores. Furthermore, we have identified a lysine degradation pathway as a common regulatory pathway for miR-1260a, miR-1260b, and miR-3182 by using DIANA-mirPath. PMID:26743126

  12. Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.

    PubMed

    Lafosse, Laurent; Baier, Gloria P; Leuzinger, Jan

    2005-08-01

    This article presents an all-arthroscopic technique for coracoclavicular ligament reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint dislocation. A coracoacromial ligament transfer is done to reconstruct the torn coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament is dissected from the undersurface of the acromion and is reinserted on the inferior clavicle by transosseous suture fixation. Additional wire or screw stabilization may be used. With this method, we achieve a very satisfactory reduction of the dislocated acromioclavicular joint. PMID:16086572

  13. Acute Pneumonia.

    PubMed

    Arshad, Hammad; Fasanya, Adebayo; Cheema, Tariq; Singh, Anil C

    2016-01-01

    Acute pneumonia is an active infection of the lungs that results when an individual at risk gets exposed to a particular microbiological pathogen. Acute pneumonia is the leading cause of death in the United States that is attributable to an infection. The risk factors, pathogenesis, and microbiological organisms involved differ if the pneumonia develops in the community versus health care-associated environment. The development of concise and comprehensive guidelines has led to an improvement in the management of the problem. However, the emergence of multidrug-resistant organisms and the increase in the percentage of elderly population keep mortality risk very substantial. PMID:26919676

  14. Analyzing MiRNA-LncRNA Interactions.

    PubMed

    Paraskevopoulou, Maria D; Hatzigeorgiou, Artemis G

    2016-01-01

    Long noncoding RNAs (lncRNAs) are noncoding transcripts usually longer than 200 nts that have recently emerged as one of the largest and significantly diverse RNA families. The biological role and functions of lncRNAs are still mostly uncharacterized. Their target-mimetic, sponge/decoy function on microRNAs was recently uncovered. miRNAs are a class of noncoding RNA species (~22 nts) that play a central role in posttranscriptional regulation of protein coding genes by mRNA cleavage, direct translational repression and/or mRNA destabilization. LncRNAs can act as miRNA sponges, reducing their regulatory effect on mRNAs. This function introduces an extra layer of complexity in the miRNA-target interaction network. This chapter focuses on the study of miRNA-lncRNA interactions with either in silico or experimentally supported analyses. The proposed methodologies can be appropriately adapted in order to become the backbone of advanced multistep functional miRNA analyses. PMID:26721498

  15. Acute Myocardial Infarction Due to Spontaneous Dissection of the Right Coronary Artery in a Young Male

    SciTech Connect

    Papadopoulos, Dimitris P. Moyssakis, Ioannis; Perakis, Alexandros; Athanasiou, Andreas; Anagnostopoulou, Sophia; Benos, Ioannis; Votteas, Vassilios E.

    2004-09-15

    Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. We report a case of a 33-year-old male who presented with an acute inferior myocardial infarction. Coronary arteriography performed 3 hours after the episode revealed a dissection involving the middle segment of right coronary artery. Because of a spiral form of dissection and the TIMI 3 flow grade, our patient was treated medically and repeat coronary angiography 6 months later was decided.

  16. Takotsubo cardiomyopathy after acute myocardial infarction: An unusual case of possible association.

    PubMed

    Ferrara, Francesco; Baldi, Cesare; Malinconico, Marisa; Acri, Edvige; Cirillo, Annapaola; Citro, Rodolfo; Bossone, Eduardo

    2016-04-01

    Takotsubo cardiomyopathy is an acute reversible clinical condition mimicking an acute myocardial infarction. Although a normal coronary artery tree is frequently detected, the concurrence of coronary artery disease is a common finding in a substantial proportion of patients. We report an unusual case of takotsubo cardiomyopathy in post-menopausal women after emotional stress, occurring after inferior ST-segment elevation myocardial infarction. The possible association between takotsubo cardiomyopathy and coronary artery disease is discussed. PMID:24833638

  17. Efficacy of Lower-Extremity Venous Thrombolysis in the Setting of Congenital Absence or Atresia of the Inferior Vena Cava

    SciTech Connect

    Ganguli, Suvranu Kalva, Sanjeeva; Oklu, Rahmi; Walker, T. Gregory; Datta, Neil; Grabowski, Eric F.; Wicky, Stephan

    2012-10-15

    Purpose: A rare but described risk factor for deep venous thrombosis (DVT), predominately in the young, is congenital agenesis or atresia of the inferior vena cava (IVC). The optimal management for DVT in this subset of patients is unknown. We evaluated the efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) followed by systemic anticoagulation in the treatment of acute lower-extremity DVT in the setting of congenital IVC agenesis or atresia. Materials and Methods: Between November of 2005 and May of 2010, six patients (three women [average age 21 years]) were referred to our department with acute lower-extremity DVT and subsequently found to have IVC agenesis or atresia on magnetic resonance imaging. A standardized technique for PCDT (the Angiojet Rheolytic Thrombectomy System followed by the EKOS Microsonic Accelerated Thrombolysis System) was used for all subjects. Successful thrombolysis was followed by systemic heparinization with transition to Coumadin or low molecular-weight heparin and compression stockings. Subjects were followed-up at 1, 3, and then every 6 months after the procedure with clinical assessment and bilateral lower-extremity venous ultrasound. Results: All PCDT procedures were technically successful. No venous stenting or angioplasty was performed. The average thrombolysis time was 28.6 h (range 12-72). Two patients experienced heparin-induced thrombocytopenia, and one patient developed a self-limited knee hemarthrosis, No patients were lost to follow-up. The average length of follow-up was 25.8 {+-} 20.2 months (range 3.8-54.8). No incidence of recurrent DVT was identified. There were no manifestations of postthrombotic syndrome. Conclusions: PCDT followed by systemic anticoagulation and the use of compression stockings appears to be safe and effective in relatively long-term follow-up treatment of patients who present with acute DVT and IVC agenesis or atresia.

  18. The regulation roles of miR-125b, miR-221 and miR-27b in porcine Salmonella infection signalling pathway

    PubMed Central

    Yao, Min; Gao, Weihua; Yang, Jun; Liang, Xiongyan; Luo, Jingbo; Huang, Tinghua

    2016-01-01

    miRNAs are non-coding RNA molecules typically 18–22 nucleotides long that can suppress the expression of their target genes. Several laboratories have attempted to identify miRNAs from the pig that are involved in Salmonella infection. These bioinformatics strategies using the newly available genomic sequence are generally successful. Here, we report an in silico identification of miRNAs in pig focusing on the Salmonella infection pathway, and further investigated the differential expression of those miRNAs by quantitative real-time PCR during pre- and post-natal stage of Salmonella inoculation from the peripheral blood of commercially breed pigs. We identified 29 miRNAs that have predicted targets in the Salmonella infection pathway and nine of them were not yet described in pig. In addition, the expression of nine selected miRNAs was validated in the peripheral blood by northern blotting. Through expression analyses, differences were found between pre- and post-natal stages of Salmonella inoculation for miR-221, miR-125b and miR-27b—all of them were suppressed 2 days after Salmonella inoculation. The predicted targets of those three miRNAs were validated by luciferase reporter assays. We show that FOS is a direct target of miR-221, miR-125b can suppress MAPK14, and miR-27b can target IFNG. These findings will be helpful in understanding the function and processing of these miRNAs in Salmonella infection. The miRNA differentially expressed in the peripheral blood of commercial breed pigs suggest that it can be used as genetic markers for salmonella infection resistance in pigs. PMID:27474500

  19. MiRNA-146a regulates the maturation and differentiation of vascular smooth muscle cells by targeting NF-κB expression.

    PubMed

    Dong, Shaohong; Xiong, Wei; Yuan, Jianhui; Li, Jianghua; Liu, Jianjun; Xu, Xinyun

    2013-08-01

    Dysfunction of vascular smooth muscle cells (VSMCs) is key in the pathogenesis of proliferative cardiovascular diseases, including atherosclerosis and post-angioplasty restenosis. However, to date, the molecular mechanisms of this pathological process have not been elucidated. Growing evidence indicates that microRNAs (miRNAs) are a class of novel gene regulators. Recently, miR-146a was shown to be highly expressed in rat balloon-injured vascular walls as well as in peripheral blood mononuclear cells (PBMCs) from patients with acute coronary syndrome (ACS). The aim of the present study was to investigate the role of miR-146a in regulating VSMC fate and the possible underlying mechanisms involved. Our results revealed that the expression of miR‑146a was increased in proliferative VSMCs. Subsequently, we observed that the knockdown of miR‑146a significantly inhibited the proliferative and migratory properties of VSMCs in vitro, while it markedly promoted the apoptotic capacity of VSMCs. In addition, we demonstrated that the protein expression of nuclear factor-κBp65 (NF-κBp65) and the proliferative cell nuclear antigen (PCNA), known as critical transcriptional factors, were downregulated. By contrast, the crucial proapoptotic molecule Bax has been revealed to be upregulated following miR‑146a knockdown. These results support the conclusion that miR-146a is a novel regulator of VSMC fate and may be a new biomarker or therapeutic target for proliferative cardiovascular disease. PMID:23784108

  20. Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

    PubMed Central

    Selvamani, Amutha; Williams, Madison H.; Miranda, Rajesh C.; Sohrabji, Farida

    2015-01-01

    Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11–12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity. PMID:24428837

  1. A Case of Behçet’s Disease with Superior and Inferior Vena Caval Occlusion

    PubMed Central

    Yoo, Wan-Hee; Moon, Jin-Seong; Kim, Sung-Il; Kim, Wan-Uk; Min, Jun-Gi; Park, Sung-Hwan; Lee, Sang-Heon; Cho, Chul-Soo; Kim, Ho-Yeon

    1998-01-01

    Behçet’s disease is a chronic multisystemic disorder involving many organs and characterized by recurrent oral and genital ulcers and relapsing iritis. A case of BD with large vein thrombosis involving superior and inferior vena cava is presented. Large vein thrombosis in BD is not commonly developed and most commonly observed in the inferior or superior vena cava. A review of the literature emphasizes the rarity of the combined superior and inferior vena caval occlusion. Existence of extensive large vein occlusion in BD is associated with limited therapy and poor prognosis. PMID:9735671

  2. Inferior vena cava leiomyosarcoma confirmed by catheter suction biopsy during digital subtraction angiography.

    PubMed

    Wei, Ning; Xu, Xiang-Dong; Xu, Hao; Zu, Mao-Heng

    2014-01-01

    Leiomyosarcoma of vascular origin is a rare disease and most cases arise in the inferior vena cava. Inferior vena cava leiomyosarcoma (IVCLMS) usually presents in females in their sixth decade of life. The clinical symptoms are often non-specific and the diagnosis is often delayed. Current imaging techniques can accurately differentiate inferior vena cava neoplasms from other non-neoplastic lesions. However, definitive diagnosis of IVCLMS needs histologic evidence. We report a case of IVCLMS in a 61-year old Chinese woman. This is the first IVCLMS case confirmed by catheter suction biopsy during digital subtraction angiography. PMID:25232438

  3. Influence of hematoma location on acute mortality after intracerebral hemorrhage

    PubMed Central

    Lee, Ji-Yong; King, Caroline; Stradling, Dana; Warren, Michael; Nguyen, Dennis; Lee, Johnny; Riola, Mark A.; Montoya, Ricardo; Patel, Dipika; Le, Vu H.; Welbourne, Susan J.; Cramer, Steven C.

    2012-01-01

    Background and Purpose The current study aimed to identify predictors of acute mortality after intracerebral hemorrhage (ICH), including voxel-wise analysis of hematoma location. Methods In 282 consecutive patients with acute ICH, clinical and radiological predictors of acute mortality were identified. Voxel-based lesion-symptom mapping examined spatial correlates of acute mortality, contrasting results in basal ganglia ICH and lobar ICH. Results Acute mortality was 47.9%. In bivariate analyses, one clinical (serum glucose) and two radiological (hematoma volume and intraventricular extension) measures significantly predicted mortality. The relationship was strongest for hematoma volume. Multivariable modeling identified four significant predictors of mortality (ICH volume, intraventricular extension, serum glucose, and serum hemoglobin), although this model only minimally improved the predictive value provided by ICH volume alone. Voxel-wise analysis found that for patients with lobar ICH, brain regions where acute hematoma was significantly associated with higher acute mortality included inferior parietal lobule and posterior insula; for patients with basal ganglia ICH, a large region extending from cortex to brainstem. Conclusions For patients with lobar ICH, acute mortality is related to both hematoma size and location, with findings potentially useful for therapeutic decision-making. The current findings also underscore differences between the syndromes of acute deep and lobar ICH. PMID:23279617

  4. TREM-1-accentuated lung injury via miR-155 is inhibited by LP17 nanomedicine.

    PubMed

    Yuan, Zhihong; Syed, Mansoor; Panchal, Dipti; Joo, Myungsoo; Bedi, Chetna; Lim, Sokbee; Onyuksel, Hayat; Rubinstein, Israel; Colonna, Marco; Sadikot, Ruxana T

    2016-03-01

    Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. Synergy between TREM-1 and Toll-like receptor amplifies the inflammatory response; however, the mechanisms by which TREM-1 accentuates inflammation are not fully understood. In this study, we investigated the role of TREM-1 in a model of LPS-induced lung injury and neutrophilic inflammation. We show that TREM-1 is induced in lungs of mice with LPS-induced acute neutrophilic inflammation. TREM-1 knockout mice showed an improved survival after lethal doses of LPS with an attenuated inflammatory response in the lungs. Deletion of TREM-1 gene resulted in significantly reduced neutrophils and proinflammatory cytokines and chemokines, particularly IL-1β, TNF-α, and IL-6. Physiologically deletion of TREM-1 conferred an immunometabolic advantage with low oxygen consumption rate (OCR) sparing the respiratory capacity of macrophages challenged with LPS. Furthermore, we show that TREM-1 deletion results in significant attenuation of expression of miR-155 in macrophages and lungs of mice treated with LPS. Experiments with antagomir-155 confirmed that TREM-1-mediated changes were indeed dependent on miR-155 and are mediated by downregulation of suppressor of cytokine signaling-1 (SOCS-1) a key miR-155 target. These data for the first time show that TREM-1 accentuates inflammatory response by inducing the expression of miR-155 in macrophages and suggest a novel mechanism by which TREM-1 signaling contributes to lung injury. Inhibition of TREM-1 using a nanomicellar approach resulted in ablation of neutrophilic inflammation suggesting that TREM-1 inhibition is a potential therapeutic target for neutrophilic lung inflammation and acute respiratory distress syndrome (ARDS). PMID:26684249

  5. A path-based measurement for human miRNA functional similarities using miRNA-disease associations.

    PubMed

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-01-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity. PMID:27585796

  6. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    PubMed Central

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-01-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity. PMID:27585796

  7. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  8. Influence of ApoB100 3′ hypervariable repeats on acute myocardial infarction

    PubMed Central

    Singh, Neha; Sinha, Nakul; Kumar, Sudeep; Pandey, Chandra M; Agrawal, Suraksha

    2014-01-01

    Background and objective The 3′ flanking region of apolipoprotein B (ApoB) 100 gene is known to contain short A+T-rich DNA sequences which are hypervariable in nature and called the variable number of tandem repeats (VNTRs). It results in different alleles of ApoB100. The present study extends the investigation of whether there is a correlation between the presence of these alleles and acute myocardial infarction (MI). Methods We examined ApoB genotypes in 230 acute MI patients and 300 healthy controls. PCR based genotyping was done for ApoB 3′ VNTRs. Results We recoded 3′ApoB-VNTR alleles through three- and five-allelic models based on different sizes and found that large repeats (>37) were significantly associated with acute MI (p<0.0001). These large repeats (>37) were also significantly associated with higher lipid levels in the MI group. Conclusion Patients with 3′ApoB-VNTR large repeats (>37) are more susceptible to acute MI development.

  9. miR-221 overexpression contributes to liver tumorigenesis.

    PubMed

    Pineau, Pascal; Volinia, Stefano; McJunkin, Katherine; Marchio, Agnès; Battiston, Carlo; Terris, Benoît; Mazzaferro, Vincenzo; Lowe, Scott W; Croce, Carlo M; Dejean, Anne

    2010-01-01

    MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment. PMID:20018759

  10. miR-221 overexpression contributes to liver tumorigenesis

    PubMed Central

    Pineau, Pascal; Volinia, Stefano; McJunkin, Katherine; Marchio, Agnès; Battiston, Carlo; Terris, Benoît; Mazzaferro, Vincenzo; Lowe, Scott W.; Croce, Carlo M.; Dejean, Anne

    2009-01-01

    MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment. PMID:20018759

  11. miReg: a resource for microRNA regulation.

    PubMed

    Barh, Debmalya; Bhat, Dattatraya; Viero, Cedric

    2010-01-01

    MicroRNAs (miRNAs/miRs) are important cellular components that regulate gene expression at posttranscriptional level. Various upstream components regulate miR expression and any deregulation causes disease conditions. Therefore, understanding of miR regulatory network both at upstream and downstream level is crucial and a resource on this aspect will be helpful. Currently available miR databases are mostly related to downstream targets, sequences, or diseases. But as of now, no database is available that provides a complete picture of miR regulation in a specific condition. Our miR regulation web resource (miReg) is a manually curated one that represents validated upstream regulators (transcription factor, drug, physical, and chemical) along with downstream targets, associated biological process, experimental condition or disease state, up or down regulation of the miR in that condition, and corresponding PubMed references in a graphical and user friendly manner, browseable through 5 browsing options. We have presented exact facts that have been described in the corresponding literature in relation to a given miR, whether it's a feed-back/feed-forward loop or inhibition/activation. Moreover we have given various links to integrate data and to get a complete picture on any miR listed. Current version (Version 1.0) of miReg contains 47 important human miRs with 295 relations using 190 absolute references. We have also provided an example on usefulness of miReg to establish signalling pathways involved in cardiomyopathy. We believe that miReg will be an essential miRNA knowledge base to research community, with its continuous upgrade and data enrichment. This HTML based miReg can be accessed from: www.iioab-mireg.webs.com or www.iioab.webs.com/mireg.htm. PMID:20693604

  12. Clinical Sequelae of Thrombus in an Inferior Vena Cava Filter

    SciTech Connect

    Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan; Kalva, Sanjeeva P.

    2010-04-15

    The purpose of this study was to assess the long-term clinical sequelae of inferior vena cava (IVC) filter thrombus and the effect of anticoagulation on filter thrombus. Of 1,718 patients who had IVC filters placed during 2001-2008, 598 (34.8%) had follow-up abdominal CT. Filter thrombus was seen in 111 of the 598 (18.6%). There were 44 men (39.6%). The mean age at filter placement was 64 years. The medical diseases included cancer in 64, trauma in 15, stroke in 12, and others in 20. The frequency of filter thrombus on CT and asymptomatic filter thrombus on CT was calculated. The frequency of pulmonary embolism (PE) in patients with filter thrombus was calculated. The frequency of thrombus progression or regression (on CT, available in 56) was calculated. The effect of anticoagulation on filter thrombus regression/progression was evaluated using the Fisher exact test by comparing the group of patients who received anticoagulants versus those who did not. A P-value of <0.05 was considered significant. The overall frequency of filter thrombus was 18.6%. Total occlusion of the IVC filter was seen in 12 of 598 (2%). The filter thrombus was asymptomatic in 110 (18.3%). Filter thrombus was detected after a median of 35 days (range, 0-2082) following filter placement. Thrombus extended above the filter in 4 (3.6%); IVC thrombus below the filter was seen in 35(31.5%). Thrombus in the filter occluded <25% of the filter volume in 58 (52.3%), 25-50% in 21 (18.9%), and 50-75% in 20 (18%). Total IVC occlusion was seen in 12 (10.8%). Eighty-three patients received anticoagulation. Sixteen patients developed symptoms of PE. PE was confirmed on CT in 3 of 15 (2.7%). On follow-up, filter thrombus regressed completely in 19 (33.9%) after a median of 6 months. Filter thrombus decreased in size in 13 (23.2%) and it progressed without IVC occlusion in 7 (12.6%). In one (1.7%), filter thrombus progressed to IVC occlusion. Filter thrombus remained stable in 16 (28.6%). There was no

  13. The representation of stimulus familiarity in anterior inferior temporal cortex.

    PubMed

    Li, L; Miller, E K; Desimone, R

    1993-06-01

    1. The inferior temporal (IT) cortex plays an important role in both short- and long-term memory for visual patterns. Most previous studies of IT neurons have tested their responses in recency memory tasks, which require that the memory lasts only the length of a single behavioral trial, which may be < 1 s. To determine the role of IT neurons in longer lasting memories, we measured their responses to initially novel stimuli as the stimuli gradually became familiar to the animal. 2. Two rhesus monkeys were trained on a delayed matching to sample (DMS) task with several intervening stimuli between the sample and the final matching stimulus on each trial. The purpose of the task was to ensure that the animal attended to the stimuli and held them in memory, at least temporarily. Unlike in several previous studies, the focus was not on within-trial effects but rather on the incidental memories that built up across trials as the stimuli became familiar. Each cell was tested with a set of 20 novel stimuli (digitized pictures of objects) that the monkey had not seen before. These stimuli were used in a fixed order over the course of an hour-long recording session, and the number of intervening trials between repetitions of a given sample stimulus was varied. 3. The responses of about one-third of the cells recorded in anterior-ventral IT cortex declined systematically as the novel stimuli became familiar. After six to eight repetitions, responses reached a plateau that was approximately 40% of the peak response. Virtually all of these cells also showed selectivity for particular visual stimuli and thus were not "novelty detectors" in the sense of cells that respond to any novel stimulus. Rather, the responses of these cells were a joint function of familiarity and specific object features such as shape and color. A few cells showed increasing responses with repetition over the recording session, but these changes were accompanied by changes in baseline firing rate

  14. Identification of Aberrantly Expressed miRNAs in Gastric Cancer

    PubMed Central

    Liu, Dan; Hu, Xiaowei; Zhou, Hongfeng; Shi, Guangyue; Wu, Jin

    2014-01-01

    The noncoding components of the genome, including miRNA, can contribute to pathogenesis of gastric cancer. Their expression has been profiled in many human cancers, but there are a few published studies in gastric cancer. It is necessary to identify novel aberrantly expressed miRNAs in gastric cancer. In this study, the expression profile of 1891 miRNAs was analyzed using a miRCURY array LNA miRNA chip from three gastric cancer tissues and three normal tissues. The expression levels of 4 miRNAs were compared by real-time PCR between cancerous and normal tissues. We found that 31 miRNAs are upregulated in gastric cancer (P < 0.05) and 10 miRNAs have never been reported by other studies; 30 miRNA are downregulated (P < 0.05) in gastric cancer tissues. Gene ontology analysis revealed that those dysregulated miRNAs mainly take part in regulating cell proliferation. The levels of has-miR-105, -213∗, -514b, and -548n were tested by real-time PCR and have high levels in cancerous tissues. Here, we report a miRNA profile of gastric cancer and provide new perspective to understand this malignant disease. This novel information suggests the potential roles of these miRNAs in the diagnosis, prognosis biomarkers, or therapy targets of gastric cancer. PMID:24982669

  15. miRNA expression during prickly pear cactus fruit development.

    PubMed

    Rosas-Cárdenas, Flor de Fátima; Caballero-Pérez, Juan; Gutiérrez-Ramos, Ximena; Marsch-Martínez, Nayelli; Cruz-Hernández, Andrés; de Folter, Stefan

    2015-02-01

    miRNAs are a class of small non-coding RNAs that regulate gene expression. They are involved in the control of many developmental processes, including fruit development. The increasing amount of information on miRNAs, on their expression, abundance, and conservation between various species, provides a new opportunity to study the role of miRNAs in non-model plant species. In this work, we used a combination of Northern blot and tissue print hybridization analysis to identify conserved miRNAs expressed during prickly pear cactus (Opuntia ficus indica) fruit development. Comparative profiling detected the expression of 34 miRNAs, which were clustered in three different groups that were associated with the different phases of fruit development. Variation in the level of miRNA expression was observed. Gradual expression increase of several miRNAs was observed during fruit development, including miR164. miR164 was selected for stem-loop RT-PCR and for a detailed spatial-temporal expression analysis. At early floral stages, miR164 was mainly localized in meristematic tissues, boundaries and fusion zones, while it was more homogenously expressed in fruit tissues. Our results provide the first evidence of miRNA expression in the prickly pear cactus and provide the basis for future research on miRNAs in Opuntia. Moreover, our analyses suggest that miR164 plays different roles during prickly pear cactus fruit development. PMID:25366556

  16. miEAA: microRNA enrichment analysis and annotation.

    PubMed

    Backes, Christina; Khaleeq, Qurratulain T; Meese, Eckart; Keller, Andreas

    2016-07-01

    Similar to the development of gene set enrichment and gene regulatory network analysis tools over a decade ago, microRNA enrichment tools are currently gaining importance. Building on our experience with the gene set analysis toolkit GeneTrail, we implemented the miRNA Enrichment Analysis and Annotation tool (miEAA). MiEAA is a web-based application that offers a variety of commonly applied statistical tests such as over-representation analysis and miRNA set enrichment analysis, which is similar to Gene Set Enrichment Analysis. Besides the different statistical tests, miEAA also provides rich functionality in terms of miRNA categories. Altogether, over 14 000 miRNA sets have been added, including pathways, diseases, organs and target genes. Importantly, our tool can be applied for miRNA precursors as well as mature miRNAs. To make the tool as useful as possible we additionally implemented supporting tools such as converters between different miRBase versions and converters from miRNA names to precursor names. We evaluated the performance of miEAA on two sets of miRNAs that are affected in lung adenocarcinomas and have been detected by array analysis. The web-based application is freely accessible at: http://www.ccb.uni-saarland.de/mieaa_tool/. PMID:27131362

  17. miEAA: microRNA enrichment analysis and annotation