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Sample records for acute inferior mi

  1. Acute Anterior Myocardial Infarction Accompanied by Acute Inferior Myocardial Infarction: A Very Rare Coronary Artery Anomaly.

    PubMed

    Alsancak, Y; Sezenöz, B; Duran, M; Unlu, S; Turkoglu, S; Yalcın, R

    2015-01-01

    Coronary artery anomalies are rare and mostly silent in clinical practice. First manifestation of this congenital abnormality can be devastating as syncope, acute coronary syndrome, and sudden cardiac death. Herein we report a case with coronary artery anomaly complicated with ST segment myocardial infarction in both inferior and anterior walls simultaneously diagnosed during primary percutaneous coronary intervention.

  2. 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.

  3. Anterior ST segment depression in acute inferior myocardial infarction as a marker of greater inferior, apical, and posterolateral damage

    SciTech Connect

    Ruddy, T.D.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Newell, J.B.; McKusick, K.A.; Boucher, C.A.; Strauss, H.W.

    1986-12-01

    The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% (mean +/- S.E.M.) vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury.

  4. Renal Vein and Inferior Vena Cava Thrombosis: A Rare Extrasplanchnic Complication of Acute Pancreatitis

    PubMed Central

    Choksi, Dhaval; Chaubal, Alisha; Pipaliya, Nirav; Ingle, Meghraj; Sawant, Prabha

    2016-01-01

    Acute pancreatitis is an inflammatory disorder often associated with various complications. Approximately one fourth of patients with acute pancreatitis develop vascular complications, of which venous thrombosis forms a major group. Extrasplanchnic venous thrombosis is less common, and simultaneous renal vein and inferior vena cava thrombosis is reported only twice. We report a case of alcohol-related acute pancreatitis complicated by simultaneous renal vein and inferior vena cava thrombosis. PMID:28008405

  5. MiR-125b, miR-100 and miR-99a co-regulate vincristine resistance in childhood acute lymphoblastic leukemia.

    PubMed

    Akbari Moqadam, F; Lange-Turenhout, E A M; Ariës, I M; Pieters, R; den Boer, M L

    2013-10-01

    MicroRNA-125b (miR-125b), miR-99a and miR-100 are overexpressed in vincristine-resistant acute lymphoblastic leukemia (ALL). Cellular viability of ETV6-RUNX1-positive Reh cells significantly increased in presence of 9 ng/mL vincristine upon co-expression of miR-125b/miR-99a (91 ± 4%), miR-125b/miR-100 (93 ± 5%) or miR-125b/miR-99a/miR-100 (82 ± 17%) compared with miR-125b-transduced cells (38 ± 13%, P<0.05). Co-expression of these miRNAs resulted in downregulation of DNTT, NUCKS1, MALAT1, SNRPE, PNO1, SET, KIF5B, PRPS2, RPS11, RPL38 and RPL23A (fold-change 1.3-1.9, p<0.05). Similarly, 7 out of these genes are lower expressed in vincristine-resistant ALL cells of children (p<0.05). The concerted function of miR-125b in combination with miR-99a and/or miR-100 illustrates the complexity of vincristine-resistant pediatric ALL.

  6. 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.

  7. 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

  8. Clinical implications of anterior S-T segment depression in patients with acute inferior myocardial infarction

    SciTech Connect

    Croft, C.H.; Woodward, W.; Nicod, P.; Corbett, J.R.; Lewis, S.E.; Willerson, J.T.; Rude, R.E.

    1982-09-01

    To assess various factors associated with anterior S-T segment depression during acute inferior myocardial infarction, 47 consecutive patients with electrocardiographic evidence of a first transmural inferior infarction were studied prospectively with radionuclide ventriculography an average of 7.3 hours (range 2.9 to 15.3) after the onset of symptoms. Thirty-nine patients (Group I) had anterior S-T depression in the initial electrocardiogram and 8 (Group II) did not have such reciprocal changes. There was no difference between the two groups in left ventricular end-diastolic or end-diastolic volume index or left ventricular ejection fraction. Stroke volume index was greater in Group I than in Group II. There were no group differences in left ventricular total or regional wall motion scores. A weak correlation existed between the quantities (mV) or inferior S-T segment elevation and reciprocal S-T depression. No relation between anterior S-T segment depression and the left ventricular end-diastolic volume index could be demonstrated; the extent of left ventricular apical and right ventricular wall motion abnormalities, both frequently associated with inferior infarction, did not correlate with the quantity of anterior S-T depression. These data show that anterior S-T segment depression occurs commonly during the early evolution of transmural inferior infarction, is not generally a marker of functionally significant anterior ischemia and cannot be used to predict left ventricular function in individual patients. Anterior S-T segment depression may be determined by reciprocal mechanisms.

  9. Acute inferior myocardial infarction after electrical weapon exposure: case report and review of the literature.

    PubMed

    Belen, Erdal; Tipi, Fatih Fahri; Bayyiğit, Akif; Helvacı, Ayşen Şerife

    2015-03-01

    The use of conducted electrical weapons (CEWs) by legal security forces and in civil society is rapidly increasing. While they are generally considered safe devices, and fatal complications are rare, it is possible to see a small number of complications. In the present case, we describe the detection of acute inferior myocardial infarction in a patient who experienced chest pain after being exposed to a CEW. In such cases, multiple factors should be considered, and the choice of treatment and follow-up should be decided accordingly.

  10. Acute inferior myocardial infarction in a patient with a prosthetic aortic valve and high international normalized ratio

    PubMed Central

    Sari, Ibrahim; Delil, Kenan; Ileri, Cigdem; Samadov, Fuad

    2014-01-01

    ST elevation acute myocardial infarction in patients with a mechanical prosthetic valve is rare and usually due to inadequate anticoagulation. We present a case of acute inferior myocardial infarction in a patient with a prosthetic aortic valve and high international normalized ratio, which has not been reported previously. PMID:24799934

  11. 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.

  12. Sudden death due to ventricular double rupture as a complication of inferior acute myocardial infarction

    PubMed Central

    Chen, Shi-Jian; Zhang, Chen; Meng, Qing-Tao; Peng, Yong; Chen, Mao

    2016-01-01

    Abstract Rationale: Ventricular double rupture (VDR) is a rare but lethal mechanical complication of acute myocardial infarction (AMI). The early identification and timely treatment of VDR remain challenging problems. We present a case of AMI with VDR and briefly review the characteristics and prognosis of this life-threatening disease. Patient concerns and Diagnoses: A 77-year-old male presented to our hospital with a 4-day history of severe dizziness, mild chest tightness, and dyspnea. An inferior AMI was diagnosed. Interventions and Outcomes: On the second hospital day, hypotension and a new cardiac murmur was found. The emergency echocardiographic study disclosed a ventricular septal defect. Soon after that the patient suddenly died of ventricular free-wall rupture. Lessons: In patients with AMI complicated by a septal perforation in the apical region, close to the septum-free wall junction, special attention should be paid to the great risk of VDR. Other high risk factors included advanced age, delayed reperfusion, and inferior infarction. Sufficient evaluation of the risk factors, close monitoring of vital signs, early identification of the specific symptoms, and timely treatment are the key points for the effective prediction and prevention of VDR. PMID:28033290

  13. Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control

    PubMed Central

    Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan

    2013-01-01

    Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No–Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition. PMID:23673865

  14. Inferior frontal cortex modulation with an acute dose of heroin during cognitive control.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan

    2013-10-01

    Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No-Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition.

  15. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke

    PubMed Central

    Chen, Yajing; Song, Yaying; Huang, Jun; Qu, Meijie; Zhang, Yu; Geng, Jieli; Zhang, Zhijun; Liu, Jianrong; Yang, Guo-Yuan

    2017-01-01

    Recent studies have demonstrated that exosomal microRNAs (miRNAs) are novel biomarkers and therapeutic targets for various diseases including vascular disease. However, specific exosomal miRNAs expression in stroke patients has not been reported yet. Here, we explored whether circulating exosomal miRNAs can serve as potential biomarkers for the diagnosis of acute ischemic stroke and discussed the potential for clinical application. Blood samples were collected from acute ischemic stroke patients within the first 72 h (n = 50). Circulating exosomes were exacted by Exoquick exosome isolation kit and characterized by transmission electron microscopy. Western blot was performed to assess the expression of exosomal protein makers. Exosomal miRNA-223 (miR-223) was detected by RT-PCR assay. The relationship between the expression levels of miR-223 and National Institutes of Health Stroke Scale (NIHSS) scores, brain infarct volume, and neurological outcomes were analyzed. Circulating exosomes were isolated and the size of vesicles ranged between 30 and 100 nm. The identification of exosomes was further confirmed by the detection of specific exosomal protein markers CD9, CD63, and Tsg101. Exosomal miR-223 in acute ischemic stroke patients was significantly upregulated compared to control group (p < 0.001). Exosomal miR-223 level was positively correlated with NIHSS scores (r = 0.31, p = 0.03). Exosomal miR-223 expression in stroke patients with poor outcomes was higher than those with good outcomes (p < 0.05). Increased exosomal miR-223 was associated with acute ischemic stroke occurrence, stroke severity, and short-term outcomes. Future studies with large sample are needed to assess the clinical application of exosomal miR-223 as a novel biomarker for ischemic stroke diagnosis. PMID:28289400

  16. 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.

  17. 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.

  18. Targeting the RAS/MAPK pathway with miR-181a in acute myeloid leukemia

    PubMed Central

    Santhanam, Ramasamy; Eisfeld, Ann-Kathrin; Chiang, Chi-ling; Lankenau, Malori; Yu, Bo; Hoellerbauer, Pia; Jin, Yan; Tarighat, Somayeh S.; Khalife, Jihane; Walker, Alison; Perrotti, Danilo; Bloomfield, Clara D.; Wang, Hongyan; Lee, Robert J.; Lee, Ly James; Marcucci, Guido

    2016-01-01

    Deregulation of microRNAs' expression frequently occurs in acute myeloid leukemia (AML). Lower miR-181a expression is associated with worse outcomes, but the exact mechanisms by which miR-181a mediates this effect remain elusive. Aberrant activation of the RAS pathway contributes to myeloid leukemogenesis. Here, we report that miR-181a directly binds to 3′-untranslated regions (UTRs); downregulates KRAS, NRAS and MAPK1; and decreases AML growth. The delivery of miR-181a mimics to target AML cells using transferrin-targeting lipopolyplex nanoparticles (NP) increased mature miR-181a; downregulated KRAS, NRAS and MAPK1; and resulted in decreased phosphorylation of the downstream RAS effectors. NP-mediated upregulation of miR-181a led to reduced proliferation, impaired colony formation and increased sensitivity to chemotherapy. Ectopic expression of KRAS, NRAS and MAPK1 attenuated the anti-leukemic activity of miR-181a mimics, thereby validating the relevance of the deregulated miR-181a-RAS network in AML. Finally, treatment with miR-181a-NP in a murine AML model resulted in longer survival compared to mice treated with scramble-NP control. These data support that targeting the RAS-MAPK-pathway by miR-181a mimics represents a novel promising therapeutic approach for AML and possibly for other RAS-driven cancers. PMID:27517749

  19. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    PubMed

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-05

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  20. 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.

  1. miR-137 downregulates c-kit expression in acute myeloid leukemia.

    PubMed

    Hu, Yanping; Dong, Xiaolong; Chu, Guoming; Lai, Guangrui; Zhang, Bijun; Wang, Leitong; Zhao, Yanyan

    2017-02-16

    The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial. The aim of this work was to verify whether miR-137 targets c-kit and to research the biological effects of restoring miR-137 expression in leukemia cells. We found that miR-137 binds specifically to the 3'-UTR of c-kit and suppresses the expression and activities of c-kit. There is a negative correlation between miR-137 and c-kit expression in both patients and cell lines determined by screening large clinical samples. We found that miR-137 can inhibit proliferation, promote apoptosis, and induce differentiation of c-kit+ AML cells. We determined that miR-137 can participate in the leukemogenesis by regulating c-kit, which could be used as a therapeutic target for acute myeloid leukemia.

  2. Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation

    PubMed Central

    Sukma Dewi, Ihdina; Hollander, Zsuzsanna; Lam, Karen K.; McManus, Janet-Wilson; Tebbutt, Scott J.; Ng, Raymond T.; Keown, Paul A.; McMaster, Robert W.; McManus, Bruce M.; Gidlöf, Olof; Öhman, Jenny

    2017-01-01

    Background Identifying non-invasive and reliable blood-derived biomarkers for early detection of acute cellular rejection in heart transplant recipients is of great importance in clinical practice. MicroRNAs are small molecules found to be stable in serum and their expression patterns reflect both physiological and underlying pathological conditions in human. Methods We compared a group of heart transplant recipients with histologically-verified acute cellular rejection (ACR, n = 26) with a control group of heart transplant recipients without allograft rejection (NR, n = 37) by assessing the levels of a select set of microRNAs in serum specimens. Results The levels of seven microRNAs, miR-142-3p, miR-101-3p, miR-424-5p, miR-27a-3p, miR-144-3p, miR-339-3p and miR-326 were significantly higher in ACR group compared to the control group and could discriminate between patients with and without allograft rejection. MiR-142-3p and miR-101-3p had the best diagnostic test performance among the microRNAs tested. Serum levels of miR-142-3p and miR-101-3p were independent of calcineurin inhibitor levels, as measured by tacrolimus and cyclosporin; kidney function, as measured by creatinine level, and general inflammation state, as measured by CRP level. Conclusion This study demonstrated two microRNAs, miR-142-3p and miR-101-3p, that could be relevant as non-invasive diagnostic tools for identifying heart transplant patients with acute cellular rejection. PMID:28125729

  3. 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

  4. 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.

  5. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients

    PubMed Central

    Peng, Jingwen; Zhou, Xin; Chen, Xinya; Zhao, Heng; Xu, Tian; Chen, Ling; Xu, Yun

    2016-01-01

    The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS) patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01). The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications. PMID:27661079

  6. The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML)

    PubMed Central

    2013-01-01

    Background There is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia. Methods Promoter methylation status of miR-663 was investigated by methylation specific PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of miR-663 was evaluated by semi-quantitative and real-time PCR, and the relationship between expression of miR-663 and promoter methylation was confirmed using 5-aza-2’-deoxycytidine (5-Aza) demethylation reagent. Results MiR-663 was aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the promoter was significantly methylated in three AML cell lines; methylation of miR-663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)] compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These results were confirmed by both BGS and 5-Aza demethylation analysis. In addition, miR-663 transcript expression was significantly lower in AML patients, both with and without miR-663 methylation, compared to controls; however, there were no significant differences in clinical features or French-American-British (FAB) classification between patients with and without miR-663 methylation. Conclusions Expression of miR-663 was significantly lower in pediatric AML cells compared to NBM controls; furthermore, a high frequency of miR-663 promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza demethylation. These findings suggest that hypermethylation of the miR-663 promoter may be an early event in

  7. Percutaneous transluminal coronary angioplasty in a patient in cardiogenic shock due to recent anterior wall MI with history of prior inferior wall MI 15 days back.

    PubMed

    Kahali, Dhiman; Mondal, Saroj; Sadhu, Parimal

    2012-05-01

    Extensive damage of the myocardium following an acute myocardial infarction usually causes cardiogenic shock. A 66-year-old male patient was treated successfully by primary percutaneous transluminal coronary angioplasty (PTCA) following an acute anterior wall myocardial infarction with prior moderate LV systolic dysfunction and developing cardiogenic shock with intra-aortic balloon counterpulsation (IABP), ventilator support and support with four inotropic drugs in full dosage.

  8. High miR-24 expression is associated with risk of relapse and poor survival in acute leukemia

    PubMed Central

    ORGANISTA-NAVA, JORGE; GÓMEZ-GÓMEZ, YAZMÍN; ILLADES-AGUIAR, BERENICE; ALARCÓN-ROMERO, LUZ DEL CARMEN; SAAVEDRA-HERRERA, MÓNICA VIRGINIA; RIVERA-RAMÍREZ, ANA BERTHA; GARZÓN-BARRIENTOS, VÍCTOR HUGO; LEYVA-VÁZQUEZ, MARCO ANTONIO

    2015-01-01

    MicroRNAs (miRNAs) play an essential role in the development and progression of acute leukemia (AL). miR-24 promotes the survival of hematopoietic cells. However, little is known concerning the function of miR-24 in human AL. The aim of the present study was to investigate the clinical significance of miR-24 expression in AL. miR-24 expression in 147 patients with AL and 100 healthy individuals was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). The results showed that compared with the healthy individuals, the expression of miR-24 in AL patients was significantly higher (p<0.001). In addition, miR-24 was expressed at significantly higher levels in acute myeloid leukemia (AML) patients and at significantly lower levels in acute lymphoblastic leukemia (ALL) (p<0.001). More importantly, Kaplan-Meier analysis showed that AL patients with high miR-24 expression tended to have shorter overall survival (p<0.05). In the multivariate analysis stratified for known prognostic variables, miR-24 was identified as an independent prognostic marker. Our data indicated that miR-24 upregulation was associated with poor prognosis in AL. miR-24 was identified for the first time as an independent marker for predicting the clinical outcome of AL patients. PMID:25672522

  9. 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%.

  10. Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size

    PubMed Central

    Khanna, Savita; Rink, Cameron; Ghoorkhanian, Reza; Gnyawali, Surya; Heigel, Mallory; Wijesinghe, Dayanjan S; Chalfant, Charles E; Chan, Yuk Cheung; Banerjee, Jaideep; Huang, Yue; Roy, Sashwati; Sen, Chandan K

    2013-01-01

    Glutathione depletion and 12-lipoxygenase-dependent metabolism of arachidonic acid are known to be implicated in neurodegeneration associated with acute ischemic stroke. The objective of this study was to investigate the significance of miR-29 in neurodegeneration associated with acute ischemic stroke. Neural cell death caused by arachidonic acid insult of glutathione-deficient cells was preceded by a 12-lipoxygenase-dependent loss of miR-29b. Delivery of miR-29b mimic to blunt such loss was neuroprotective. miR-29b inhibition potentiated such neural cell death. 12-Lipoxygenase knockdown and inhibitors attenuated the loss of miR-29b in challenged cells. In vivo, stroke caused by middle-cerebral artery occlusion was followed by higher 12-lipoxygenase activity and loss of miR-29b as detected in laser-captured infarct site tissue. 12-Lipoxygenase knockout mice demonstrated protection against such miR loss. miR-29b gene delivery markedly attenuated stroke-induced brain lesion. Oral supplementation of α-tocotrienol, a vitamin E 12-lipoxygenase inhibitor, rescued stroke-induced loss of miR-29b and minimized lesion size. This work provides the first evidence demonstrating that loss of miR-29b at the infarct site is a key contributor to stroke lesion. Such loss is contributed by activity of the 12-lipoxygenase pathway providing maiden evidence linking arachidonic acid metabolism to miR-dependent mechanisms in stroke. PMID:23632968

  11. Multiple aneurysms of the inferior pancreaticoduodenal artery: a rare complication of acute pancreatitis.

    PubMed

    Klonaris, Chris; Psathas, Emmanouil; Katsargyris, Athanasios; Lioudaki, Stella; Chatziioannou, Achilleas; Karatzas, Theodore

    2013-01-01

    Inferior pancreaticoduodenal artery (IPDA) aneurysms are uncommon, representing nearly 2% of all visceral aneurysms, and sporadically associated with celiac artery stenosis. Multiple IPDA aneurysms have been rarely reported. We report a case of a 53-year-old female patient with a history of prior pancreatitis, who presented with two IPDA aneurysms combined with median arcuate ligament-syndrome-like stenosis of the celiac trunk. The patient was treated successfully with coil embolization under local anesthesia. The procedure is described and illustrated in detail and the advantages and technical considerations of such an approach are also being discussed.

  12. Multiple Aneurysms of the Inferior Pancreaticoduodenal Artery: A Rare Complication of Acute Pancreatitis

    PubMed Central

    Klonaris, Chris; Katsargyris, Athanasios; Lioudaki, Stella; Chatziioannou, Achilleas; Karatzas, Theodore

    2013-01-01

    Inferior pancreaticoduodenal artery (IPDA) aneurysms are uncommon, representing nearly 2% of all visceral aneurysms, and sporadically associated with celiac artery stenosis. Multiple IPDA aneurysms have been rarely reported. We report a case of a 53-year-old female patient with a history of prior pancreatitis, who presented with two IPDA aneurysms combined with median arcuate ligament-syndrome-like stenosis of the celiac trunk. The patient was treated successfully with coil embolization under local anesthesia. The procedure is described and illustrated in detail and the advantages and technical considerations of such an approach are also being discussed. PMID:23509663

  13. Cardiac Perforation by Migrated Fractured Strut of Inferior Vena Cava Filter Mimicking Acute Coronary Syndrome.

    PubMed

    Piercecchi, Chris W; Vasquez, Julio C; Kaplan, Stephen J; Hoffman, Jordan; Puskas, John D; DeLaRosa, Jacob

    2017-02-01

    We present a rare late complication after inferior vena cava filter (IVC) placement. A 52-year-old woman with an IVC presented with sudden onset of chest pain. Cardiac catheterisation and echocardiography revealed an embolised IVC filter strut penetrating the right ventricle. Endovascular retrieval was considered but deemed unsafe due to proximity to the right coronary artery and concern for migration to pulmonary circulation. Urgent removal of the strut was performed via sternotomy. The postoperative course was uneventful. Two weeks later, she was asymptomatic. Minimally invasive approaches have been described for retrieval of intact IVC filters that have migrated to the right heart but not for embolised filter fragments. We recommend traditional sternotomy as the preferred method of retrieval as it limits the likelihood of further migration or trauma.

  14. Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.

    PubMed

    Gurer, G; Sahin, G; Cekirge, S; Tan, E; Saribas, O

    2001-10-01

    The most frequent type of cerebellar infarcts involved the posterior inferior cerebellar artery (PICA) and superior cerebellar artery territories but bilateral involvement of lateral or medial branches of PICA is extremely rare. In this report, we present a 55-year-old male who admitted to hospital with vomiting, nausea and dizziness. On examination left-sided hemiparesia and ataxic gait were detected. Infarct on bilateral medial branch of PICA artery territories was found out with cranial magnetic resonance imaging (MRI) technique and 99% stenosis of the left vertebral artery was found out with digital subtraction arteriography. The patient was put on heparin treatment. After 3 weeks, his complaints and symptoms had disappeared except for mild gait ataxia.

  15. miR-196b/miR-1290 participate in the antitumor effect of resveratrol via regulation of IGFBP3 expression in acute lymphoblastic leukemia.

    PubMed

    Zhou, Wei; Wang, Shunqing; Ying, Yi; Zhou, Ruiqing; Mao, Ping

    2017-02-01

    MicroRNAs play critical roles in the progression of acute lymphoblastic leukemia (ALL). Previous studies have indicated that miR-196b and miR-1290 play critical roles in T-cell ALL (T-ALL) and B-cell ALL (B-ALL), respectively. Resveratrol, a natural edible polyphenolic phytoalexin, possesses certain anticancer activities. Nevertheless, the mechanism involved in the regulation of ALL by resveratrol is still poorly understood. The present study aimed to reveal the potential mechanism underlying the antitumor effect of resveratrol in ALL focusing on miRNAs. Research indicates that insulin-like growth factor binding protein 3 (IGFBP3) plays a critical role in the aetiology of ALL. In the present study, we first demonstrated that the expression of IGFBP3 was decreased in ALL patients. We further identified that miR-196b and miR-1290 were overexpressed in T-ALL TALL-104 and B-ALL SUP-B15 cell lines, respectively. Moreover, resveratrol markedly decreased the overexpression of miR-196b/miR-1290 and elevated IGFBP3 expression in the ALL cell lines. As an miR-196b/miR-1290 inhibitor, resveratrol was further demonstrated to exert antitumor effects on ALL cells including antiproliferation, cell cycle arrest, apoptosis and inhibition of migration. Dual-luciferase reporter assay revealed that miR-196b/miR-1290 directly bound to the 3'-untranslated (3'-UTR) region of IGFBP3 mRNA. Moreover, we observed that IGFBP3 short interfering RNA reversed the antitumor activity of resveratrol against ALL cells. Taken together, the present study provides evidence that resveratrol targets miR-196b and miR-1290 for its antitumor activity in T-ALL and B-ALL, respectively. The present study also confirms that both miR‑196b and miR-1290 target the IGFBP3 3'-UTR and are potential therapeutic targets for ALL.

  16. Ventricular septal rupture and right ventricular intramyocardial dissection secondary to acute inferior myocardial infarction.

    PubMed

    Bittencourt, Márcio Sommer; Seltmann, Martin; Muschiol, Gerd; Achenbach, Stephan

    2010-01-01

    A 61-year-old female patient presented with sub acute myocardial infarction with an occluded right coronary artery on invasive evaluation and a ventricular septal rupture on echocardiogram. Cardiac computed tomography (CT) was performed to better define the septal anatomy. As the anatomy on cardiac CT was considered unfavorable for percutaneous intervention, the patient underwent successful surgical repair.

  17. Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera

    PubMed Central

    Melgar, Silvia; Aung, Kyaw Min; Rahman, Arman; Qadri, Firdausi; Wai, Sun Nyunt; Shirin, Tahmina

    2017-01-01

    The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (P<0.009 versus controls; P = 0.03 versus convalescent stage, pairwise). Both microRNAs were mainly expressed in the epithelium. Only marginal down-regulation of target genes IRAK1 and CARD10 was seen and a weak cytokine-profile was identified in the acute infected mucosa. No elevation of microRNA levels was seen in ETEC infection. Challenge of tight monolayers with the wild type V. cholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (P<0.01). One clinical isolate caused reduction in IRAK1 levels (P<0.05) and none of the strains induced inflammatory cytokines. In contrast, secreted factors from these strains caused markedly increased levels of IL-8, IL-1β, and CARD10 (P<0.001), without inducing microRNA expression. Thus, miR-146a and miR-155 are expressed in the duodenal epithelium at the acute stage of cholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation

  18. Evaluation of miR-216a and miR-217 as potential biomarkers of acute pancreatic injury in rats and mice.

    PubMed

    Goodwin, David; Rosenzweig, Barry; Zhang, Jun; Xu, Lin; Stewart, Sharron; Thompson, Karol; Rouse, Rodney

    2014-09-01

    Mild injury of the exocrine pancreas is often asymptomatic and can be under- or mis-diagnosed. The pancreas-enriched microRNAs miR-216a and miR-217 were evaluated as potential serum biomarkers of exocrine pancreas injury in rodent models of acute pancreatitis induced by caerulein, l-arginine, and pancreatic duct ligation. Both microRNAs showed time- and dose- relevant responses to pancreatic injury and wider dynamic ranges of response than serum amylase or lipase. Pancreas-selective microRNAs were found to be relatively sensitive serum biomarkers of pancreatic injury in rodents with potentially greater specificity than the current standard assays.

  19. Overexpressed miRNA-155 dysregulates intestinal epithelial apical junctional complex in severe acute pancreatitis

    PubMed Central

    Tian, Rui; Wang, Rui-Lan; Xie, Hui; Jin, Wei; Yu, Kang-Long

    2013-01-01

    AIM: To investigate whether miRNA-155 (miR-155) dysregulates apical junctional complex (AJC) protein expression in experimental severe acute pancreatitis (SAP). METHODS: Twenty-four male BALB/c mice were randomly assigned to two groups: the SAP group (n = 12) receiving sequential intraperitoneal injection of 50 µg/kg caerulein and 10 mg/kg lipopolysaccharide over 6 h, and the control group (n = 12) receiving intraperitoneal injection of normal saline. Animals were sacrificed 3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens. Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage. Levels of serum amylase, diamine oxidase (DAO), and tumor necrosis factor (TNF)-α were determined using commercial kits. Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA. miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction. Target genes for miR-155 were predicted using the miRTarBase database, RNA22 and PicTar computational methods. Western blotting was performed to quantitate the protein expression levels of the target gene RhoA, as well as zonula occludens (ZO)-1 and E-cadherin, two AJC component proteins. RESULTS: Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage (SAP vs control, 10.0 ± 2.0 vs 3.2 ± 1.2, P < 0.01) and intestinal epithelial barrier damage (3.2 ± 0.7 vs 1.4 ± 0.7, P < 0.01). Levels of serum amylase (21.6 ± 5.1 U/mL vs 14.3 ± 4.2 U/mL, P < 0.01), DAO (21.4 ± 4.1 mg/mL vs 2.6 ± 0.8 mg/mL, P < 0.01), and TNF-α (61.0 ± 15.1 ng/mL vs 42.9 ± 13.9 ng/mL, P < 0.01) increased significantly in SAP mice compared to those in control mice. miR-155 was significantly overexpressed in SAP intestinal epithelia (1.94 ± 0.50 fold vs 1.03 ± 0.23 fold, P < 0.01), and Rho

  20. miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome.

    PubMed

    Guo, Min; Mao, Xiaobo; Ji, Qingwei; Lang, Mingjian; Li, Songnan; Peng, Yudong; Zhou, Wei; Xiong, Bo; Zeng, Qiutang

    2010-07-01

    The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR-146a is a microRNA specifically and highly expressed in Th1-driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR-146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR-146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR-146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T-bet pathway in PBMCs. In addition, this study also provided evidence that miR-146a treatment in vitro could induce the protein expression of TNF-alpha, MCP-1, NF-kappaB p65, which are key pro-inflammatory cytokines and critical transcription factor in AS. In contrast, miR-146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS.

  1. The clinical characteristics and prognostic significance of AID, miR-181b, and miR-155 expression in adult patients with de novo B-cell acute lymphoblastic leukemia.

    PubMed

    Zhou, Guangquan; Cao, Yang; Dong, Weimin; Lin, Yan; Wang, Qi; Wu, Wei; Hua, Xiaoying; Ling, Yun; Xie, Xiaobao; Hu, Shaoyan; Cen, Jiannong; Gu, Weiying

    2017-01-31

    This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL. Moreover, B-ALL patients with AID(high) or miR-181b(low) expression had a shorter overall survival (OS). AID(high) with miR-181b(low), AID(high) with miR-155(low), miR-181b(low), miR-155(low), AID(high) with miR-181b(low) and miR-155(low) expression were associated with shorter OS. Combination of the three molecules are more accurate predictors for unfavorable OS compared with univariate group. Therefore, AID, miR-181b and miR-155 provide clinical prognosis of adult de novo B-ALL patients and may refine their molecular risk classification.

  2. Consideration of QRS complex in addition to ST-segment abnormalities in the estimation of the "risk region" during acute anterior or inferior myocardial infarction.

    PubMed

    Vervaat, F E; Bouwmeester, S; van Hellemond, I E G; Wagner, G S; Gorgels, A P M

    2014-01-01

    The myocardial area at risk (MaR) is an important aspect in acute ST-elevation myocardial infarction (STEMI). It represents the myocardium at the onset of the STEMI that is ischemic and could become infarcted if no reperfusion occurs. The MaR, therefore, has clinical value because it gives an indication of the amount of myocardium that could potentially be salvaged by rapid reperfusion therapy. The most validated method for measuring the MaR is (99m)Tc-sestamibi SPECT, but this technique is not easily applied in the clinical setting. Another method that can be used for measuring the MaR is the standard ECG-based scoring system, Aldrich ST score, which is more easily applied. This ECG-based scoring system can be used to estimate the extent of acute ischemia for anterior or inferior left ventricular locations, by considering quantitative changes in the ST-segment. Deviations in the ST-segment baseline that occur following an acute coronary occlusion represent the ischemic changes in the transmurally ischemic myocardium. In most instances however, the ECG is not available at the very first moments of STEMI and as times passes the ischemic myocardium becomes necrotic with regression of the ST-segment deviation along with progressive changes of the QRS complex. Thus over the time course of the acute event, the Aldrich ST score would be expected to progressively underestimate the MaR, as was seen in studies with SPECT as gold standard; anterior STEMI (r=0.21, p=0.32) and inferior STEMI (r=0.17, p=0.36). Another standard ECG-based scoring system is the Selvester QRS score, which can be used to estimate the final infarct size by considering the quantitative changes in the QRS complex. Therefore, additional consideration of the Selvester QRS score in the acute phase could potentially provide the "component" of infarcted myocardium that is missing when the Aldrich ST score alone is used to determine the MaR in the acute phase, as was seen in studies with SPECT as gold

  3. 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

  4. Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis

    PubMed Central

    Majer, Anna; Caligiuri, Kyle A.; Gale, Kamilla K.; Niu, Yulian; Phillipson, Clark S.; Booth, Timothy F.

    2017-01-01

    Important roles of microRNAs (miRNAs) in regulating the host response during viral infection have begun to be defined. However, little is known about the functional roles of miRNAs within an in vivo acute viral encephalitis model. We therefore identified global changes in miRNA expression during acute herpes simplex virus type 1 (HSV-1) encephalitis (HSVE) in mice. We found that many of the highly upregulated miRNAs (miR-155, miR-146a and miR-15b) detected in HSV-1 infected brain tissue are known regulators of inflammation and innate immunity. We also observed upregulation of 7 members belonging to the related group of miRNAs, the miR-200 family and miR-182 cluster (miR-200/182). Using in situ hybridization, we found that these miRNAs co-localized to regions of the brain with severe HSVE-related pathology and were upregulated in various cell types including neurons. Induction was apparent but not limited to cells in which HSV-1 was detected by immunohistochemistry, suggesting possible roles of these miRNAs in the host response to viral-induced tissue damage. Bioinformatic prediction combined with gene expression profiling revealed that the induced miR-200/182 members could regulate the biosynthesis of heparan sulfate proteoglycans. Using luciferase assays, we found that miR-96, miR-141, miR-183 and miR-200c all potentially targeted the syndecan-2 gene (Sdc2), which codes for a cell surface heparan sulfate proteoglycan involved in HSV-1 cellular attachment and entry. PMID:28045967

  5. Molecular mechanisms underlying application of serum procalcitonin and stool miR-637 in prognosis of acute ischemic stroke

    PubMed Central

    Li, You-Mei; Liu, Xue-Yuan

    2016-01-01

    We and others have reported that the serum procalcitonin (PCT) level has a demonstrative role in predicting the long-term mortality after acute ischemic stroke (AIS) in Chinese population. Nevertheless, the underlying mechanisms remain ill-defined. In the current study, we further detected a close association of stool microRNA-637 (miR-637) levels with the long-term mortality after AIS in Chinese population. Moreover, the serum PCT and stool miR-637 levels appeared to be inversely correlated. AIS patients with lower levels of stool miR-637 appeared to predict more severe mortality in the long-term. Since PCT has been shown to be mainly produced by the neuroendocrine cells in the intestine, we used an intestine neuroendocrine cell line to study the relationship between miR-637 and PCT. Bioinformatics analyses showed that miR-637 targeted the 3’-UTR of PCT mRNA to inhibit its translation, and thus the levels of PCT protein production and secretion, which was proved by luciferase reporter assay. Together, our data reveal that the molecular mechanisms underlying application of serum PCT and stool miR-637 in prognosis of AIS, in which miR-637 in intestine neuroendocrine cells may be reduced during AIS to allow more PCT to be released into serum to be detected. PMID:27830008

  6. 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

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

    PubMed Central

    Han, Xiao-yu; Ji, Min; Zhou, Ying; Zhang, A-min; Wang, Hong-chun; Ma, Dao-xin; Ji, Chun-yan

    2016-01-01

    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

  8. The effect of miR-146a on STAT1 expression and apoptosis in acute lymphoblastic leukemia Jurkat cells

    PubMed Central

    Yan, Weihong; Guo, Hua; Suo, Feng; Han, Chunling; Zheng, Hua; Chen, Tong

    2017-01-01

    The effect of miR-146a-dependent regulation of STAT1 on apoptosis in acute lymphoblastic leukemia (ALL) Jurkat cells was investigated. The miR-146a mimic and miR-146a inhibitor vectors were constructed in vitro, and experimental grouping was as follows: Control group (untreated Jurkat cells), empty vector group (Jurkat cells transfected with empty vector), agonist group (Jurkat cells transfected with miR-146a mimic) and the inhibitor group (Jurkat cells transfected with miR-146a inhibitor). Western blot analysis was used to observe the expression, respectively, of STAT1, p-STAT1 and Bcl-xL, and flow cytometry was used to test apoptosis in Jurkat cells. STAT1 and p-STAT1 expression in the agonist group was higher than that in the control and empty vector groups, but lower in the inhibitor group, and differences were statistically significant (P<0.05). The rate of apoptosis in the agonist group was significantly higher than that of the control group and blank vector group, and it was significantly lower in the inhibitor group (P<0.05). As a tumor suppressor, miR-146a can regulate expression of apoptosis-promoting factor STAT1, and anti-apoptosis factor Bcl-xL, and is able to promote apoptosis of ALL Jurkat cells. PMID:28123535

  9. 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.

  10. 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

  11. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells.

    PubMed

    Kotani, Ai; Ha, Daon; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2010-03-15

    MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

  12. 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

  13. 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.

  14. Inferior vestibular neuritis.

    PubMed

    Kim, Ji-Soo; Kim, Hyo Jung

    2012-08-01

    Vestibular neuritis (VN) mostly involves the superior portion of the vestibular nerve and labyrinth. This study aimed to describe the clinical features of VN involving the inferior vestibular labyrinth and its afferents only. Of the 703 patients with a diagnosis of VN or labyrinthitis at Seoul National University Bundang Hospital from 2004 to 2010, we retrospectively recruited 9 patients (6 women, age range 15-75) with a diagnosis of isolated inferior VN. Diagnosis of isolated inferior VN was based on torsional downbeating spontaneous nystagmus, abnormal head-impulse test (HIT) for the posterior semicircular canal (PC), and abnormal cervical vestibular-evoked myogenic potentials (VEMP) in the presence of normally functioning horizontal and anterior semicircular canals, as determined by normal HIT and bithermal caloric tests. All patients presented with acute vertigo with nausea, vomiting, and imbalance. Three patients also had tinnitus and hearing loss in the involved side. The rotation axis of torsional downbeating spontaneous nystagmus was best aligned with that of the involved PC. HIT was also positive only for the involved PC. Cervical VEMP was abnormal in seven patients, and ocular VEMP was normal in all four patients tested. Ocular torsion and subjective visual vertical tests were mostly within the normal range. Since isolated inferior VN lacks the typical findings of much more prevalent superior VN, it may be mistaken for a central vestibular disorder. Recognition of this rare disorder may help avoid unnecessary workups in patients with acute vestibulopathy.

  15. Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203).

    PubMed

    Beninson, Lida A; Brown, Peter N; Loughridge, Alice B; Saludes, Jonel P; Maslanik, Thomas; Hills, Abigail K; Woodworth, Tyler; Craig, Wendy; Yin, Hang; Fleshner, Monika

    2014-01-01

    Exosomes, biologically active nanoparticles (40-100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.

  16. Acute Stressor Exposure Modifies Plasma Exosome-Associated Heat Shock Protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)

    PubMed Central

    Beninson, Lida A.; Brown, Peter N.; Loughridge, Alice B.; Saludes, Jonel P.; Maslanik, Thomas; Hills, Abigail K.; Woodworth, Tyler; Craig, Wendy; Yin, Hang; Fleshner, Monika

    2014-01-01

    Exosomes, biologically active nanoparticles (40–100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation. PMID:25259839

  17. miR-181b increases drug sensitivity in acute myeloid leukemia via targeting HMGB1 and Mcl-1.

    PubMed

    Lu, Fei; Zhang, Jingru; Ji, Min; Li, Peng; Du, Yahui; Wang, Hongchun; Zang, Shaolei; Ma, Daoxin; Sun, Xiulian; Ji, Chunyan

    2014-07-01

    Multidrug resistance (MDR) remains the major cause of disease relapse and poor prognosis in adults with acute myeloid leukemia (AML). Emerging evidence shows that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to elucidate the mechanisms through which AML patients develop drug resistance. MicroRNAs have been shown to play an important role in regulating the chemotherapy resistance in AML. A detailed understanding of the mechanisms of microRNA that are clinically relevant in AML may enhance our ability to predict and overcome drug resistance. Here, we demonstrated, for the first time, that miR-181b was decreased significantly in human multidrug-resistant leukemia cells and relapsed/refractory AML patient samples. Overexpression of miR-181b increased the sensitivity of leukemia cells to cytotoxic chemotherapeutic agents and promoted drug-induced apoptosis. Moreover, miR-181b inhibited HMGB1 and Mcl-1 expression by direct binding to their 3'-untranslated regions. In addition, HMGB1 was expressed at high levels in relapsed/refractory AML patients and suppression of HMGB1 via RNA interference sensitized multidrug-resistant leukemia cells to chemotherapy and induced apoptosis. In conclusion, these results provide a strong rationale for the development of miR-181b-based therapeutic strategies for the enhancement of efficacy in AML treatment.

  18. 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.

  19. 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.

  20. Use of a dual lumen cannula for venovenous extra corporeal membrane oxygenation in a patient with acute respiratory distress syndrome and a previously inserted inferior vena cava filter: a case report

    PubMed Central

    Palizas Jr., Fernando; García, Christian Casabella; Norese, Mariano

    2016-01-01

    Extracorporeal membrane oxygenation is used in refractory hypoxemia in many clinical settings. Thoracic trauma patients usually develop acute respiratory distress syndrome. Due to high risk of bleeding, thrombotic complications present in this context are particularly difficult to manage and usually require insertion of an inferior vena cava filter to prevent embolism from the distal veins to the pulmonary circulation. Here, we present a case of a thoracic trauma patient with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation via a right internal jugular double lumen cannula due to a previously inserted inferior vena cava filter caused by distal bilateral calf muscle vein deep vein thrombosis. PMID:27096680

  1. Identification of miRNAs and their targets in wild tomato at moderately and acutely elevated temperatures by high-throughput sequencing and degradome analysis

    PubMed Central

    Zhou, Rong; Wang, Qian; Jiang, Fangling; Cao, Xue; Sun, Mintao; Liu, Min; Wu, Zhen

    2016-01-01

    MicroRNAs (miRNAs) are 19–24 nucleotide (nt) noncoding RNAs that play important roles in abiotic stress responses in plants. High temperatures have been the subject of considerable attention due to their negative effects on plant growth and development. Heat-responsive miRNAs have been identified in some plants. However, there have been no reports on the global identification of miRNAs and their targets in tomato at high temperatures, especially at different elevated temperatures. Here, three small-RNA libraries and three degradome libraries were constructed from the leaves of the heat-tolerant tomato at normal, moderately and acutely elevated temperatures (26/18 °C, 33/33 °C and 40/40 °C, respectively). Following high-throughput sequencing, 662 conserved and 97 novel miRNAs were identified in total with 469 conserved and 91 novel miRNAs shared in the three small-RNA libraries. Of these miRNAs, 96 and 150 miRNAs were responsive to the moderately and acutely elevated temperature, respectively. Following degradome sequencing, 349 sequences were identified as targets of 138 conserved miRNAs, and 13 sequences were identified as targets of eight novel miRNAs. The expression levels of seven miRNAs and six target genes obtained by quantitative real-time PCR (qRT-PCR) were largely consistent with the sequencing results. This study enriches the number of heat-responsive miRNAs and lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in tomatoes at elevated temperatures. PMID:27653374

  2. Acute myocardial infarction as a finding of acute promyelocytic leukemia-related coagulation disorder.

    PubMed

    Özkurt, Zübeyde N; Aypar, Eda; Sarifakiogullari, Serpil; Taçoy, Gülten; Özdag, Murat; Kahraman, Seda; Çengel, Atiye

    2015-12-01

    Acute promyelocytic leukemia (APL) has one of the most favorable prognoses among other leukemia subtypes. However, the major cause of mortality in APL is disseminated intravascular coagulation at the presentation. We present a case of acute myocardial infarction (MI) at the time of APL diagnosis before treatment. The patient suffered from chest pain, sweating and giddiness. He was hypoxic, hypotensive and bradycardic. ECG showed inferior MI. Unfractioned heparin infusion (850 U/h) was started and 5 min after the previous ECG showed total ST resolution. We suggest that in this case, MI was not related to atherosclerotic plaque rupture but related to DIC manifestation.

  3. Compression of the medulla oblongata and acute respiratory failure caused by rupture of a thrombosed large aneurysm of the anterior inferior cerebellar artery.

    PubMed

    Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Tanahashi, Kuniaki

    2010-01-01

    A 65-year-old female presented with an extremely rare case of a ruptured thrombosed large aneurysm of the anterior inferior cerebellar artery (AICA) in which a local hematoma compressed the medulla oblongata and caused acute respiratory failure. She first presented with dizziness, general fatigue, and nausea 2 months before admission. She was hospitalized for intense general fatigue, nausea, and occipitalgia. Computed tomography and T(1)-weighted magnetic resonance imaging showed a heterogeneous lesion around the right cerebello-medullary cistern. Angiography revealed a fusiform aneurysm of the right AICA. Asphyxia occurred 4 days after admission and the patient underwent an emergency operation. No subarachnoid hematoma was present, but a hematoma around the ruptured portion markedly compressed the medulla oblongata. The medulla oblongata was adequately decompressed after subtotal removal of the aneurysm. The patient's respiratory status and consciousness level recovered after the operation.

  4. 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.

  5. Inducing cell proliferative prevention in human acute promyelocytic leukemia by miR-182 inhibition through modulation of CASP9 expression.

    PubMed

    Fasihi-Ramandi, Mahdi; Moridnia, Abbas; Najafi, Ali; Sharifi, Mohammadreza

    2017-03-11

    MicroRNAs (miRNAs) are one class of endogenous non-coding RNAs that involved in post-transcriptional regulation of the gene. MiRNAs through interaction with messenger RNA (mRNA) involved in several biological processes such as cell cycle, differentiation, growth, metabolism, aging and apoptosis. MiRNAs may act as an oncogene or a tumor suppressor via up or down regulation in cancerous cells. MiR-182 located in a miR-183/-96/-182 cluster, this is the highly conserved cluster to have an important role in cancer development and tumorigenesis. Abnormal expression of miR-182 in a variety of human cancers has reported. Oncogenic features of miR-182 confirmed through negative regulation of various tumor suppressor genes. In this study, miR-182 inhibition in acute promyelocytic leukemia (APL) cell line (HL60) was performed by locked nucleic acid (LNA) anti-miR. MTT assay in three-time points 24, 48 and 72h after LNA-anti-miR-182 transfection was performed. Our study demonstrated inhibition of miR-182 can expansively decrease cell proliferation of APL cells. The Western blotting analysis presents that CASP9 expression associated with inhibition of miR-182. CASP9 protein has an important role in the mitochondrial cell death pathway as the initiator of apoptosis. These results can offer a way for inhibition of APL cells proliferates and produce translational medicine based on microgenomics and antisense therapy.

  6. Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis

    PubMed Central

    Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

    2016-01-01

    Introduction This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. Design A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Participants Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Interventions Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Analysis Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. Ethics and dissemination The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. Trial

  7. 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

  8. Uncovering low-dimensional, miR-based signatures of acute myeloid and lymphoblastic leukemias with a machine-learning-driven network approach

    PubMed Central

    Candia, Julián; Cherukuri, Srujana; Guo, Yin; Doshi, Kshama A.; Banavar, Jayanth R.; Civin, Curt I.; Losert, Wolfgang

    2016-01-01

    Complex phenotypic differences among different acute leukemias cannot be fully captured by analyzing the expression levels of one single molecule, such as a miR, at a time, but requires systematic analysis of large sets of miRs. While a popular approach for analysis of such datasets is principal component analysis (PCA), this method is not designed to optimally discriminate different phenotypes. Moreover, PCA and other low-dimensional representation methods yield linear or non-linear combinations of all measured miRs. Global human miR expression was measured in AML, B-ALL, and TALL cell lines and patient RNA samples. By systematically applying support vector machines to all measured miRs taken in dyad and triad groups, we built miR networks using cell line data and validated our findings with primary patient samples. All the coordinately transcribed members of the miR-23a cluster (which includes also miR-24 and miR-27a), known to function as tumor suppressors of acute leukemias, appeared in the AML, B-ALL and T-ALL centric networks. Subsequent qRT-PCR analysis showed that the most connected miR in the B-ALL-centric network, miR-708, is highly and specifically expressed in B-ALLs, suggesting that miR-708 might serve as a biomarker for B-ALL. This approach is systematic, quantitative, scalable, and unbiased. Rather than a single signature, our approach yields a network of signatures reflecting the redundant nature of biological signaling pathways. The network representation allows for visual analysis of all signatures by an expert and for future integration of additional information. Furthermore, each signature involves only small sets of miRs, such as dyads and triads, which are well suited for in depth validation through laboratory experiments. In particular, loss-and gain-of-function assays designed to drive changes in leukemia cell survival, proliferation and differentiation will benefit from the identification of multi-miR signatures that characterize leukemia

  9. Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Duan, Yanhong; Zhou, Min; Xiao, Jian; Wu, Chaomin; Zhou, Lei; Zhou, Feng; Du, Chunling; Song, Yuanlin

    2016-01-01

    The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein-protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD. PMID:28025995

  10. 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

  11. A Regulatory miRNA–mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury

    PubMed Central

    de Almeida, Danilo Candido; Bassi, Ênio Jose; Azevedo, Hatylas; Anderson, Letícia; Origassa, Clarice Silvia Taemi; Cenedeze, Marcos Antônio; de Andrade-Oliveira, Vinicius; Felizardo, Raphael José Ferreira; da Silva, Reinaldo Correia; Hiyane, Meire Ioshie; Semedo, Patricia; dos Reis, Marlene Antônia; Moreira-Filho, Carlos Alberto; Verjovski-Almeida, Sergio; Pacheco-Silva, Álvaro; Câmara, Niels Olsen Saraiva

    2017-01-01

    Mesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidenced in vivo and in vitro by modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-β, fibrosis, and epithelial–mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA–mRNA network. PMID:28096802

  12. c-Myc suppresses miR-451⊣YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia

    PubMed Central

    Su, Rui; Gong, Jia-Nan; Chen, Ming-Tai; Song, Li; Shen, Chao; Zhang, Xin-Hua; Yin, Xiao-Lin; Ning, Hong-Mei; Liu, Bing; Wang, Fang; Ma, Yan-Ni; Zhao, Hua-Lu; Yu, Jia; Zhang, Jun-Wu

    2016-01-01

    Aberrant activation of c-Myc plays an important oncogenic role via regulating a series of coding and non-coding genes in acute myeloid leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone and regulate gene expression via changing chromatin structure. Here, we found miR-451 is abnormally down-regulated in AML patient samples; c-Myc recruits HDAC3 to form a transcriptional suppressor complex, co-localizes on the miR-451 promoter, epigenetically inhibits its transcription and finally induces its downregulation in AML. Furthermore, our in vitro and in vivo results suggest that miR-451 functions as a tumor suppressor via promoting apoptosis and suppressing malignant cell proliferation. The mechanistic study demonstrated that miR-451 directly targets YWHAZ mRNA and suppresses YWHAZ/AKT signaling in AML. Knockdown of c-Myc results in restoration of miR-451 and inhibition of YWHAZ/AKT signaling. In AML patients, low level of miR-451 is negatively correlated with high levels of c-Myc and YWHAZ, while c-Myc level is positively related to YWHAZ expression. These results suggested that c-Myc⊣miR-451⊣YWHAZ/AKT cascade might play a crucial role during leukemogenesis, and reintroduction of miR-451 could be as a potential strategy for AML therapy. PMID:27764807

  13. Upregulation of miR-99a is associated with poor prognosis of acute myeloid leukemia and promotes myeloid leukemia cell expansion

    PubMed Central

    Si, Xiaohui; Zhang, Xiaoyun; Hao, Xing; Li, Yunan; Chen, Zizhen; Ding, Yahui; Shi, Hui; Bai, Jie; Gao, Yingdai; Cheng, Tao; Yang, Feng-Chun; Zhou, Yuan

    2016-01-01

    Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients. Ectopic expression of miR-99a led to increased colony forming ability and expansion in myeloid leukemia cells after exposure to chemotherapeutic drugs in vitro and in vivo, partially due to overcoming of chemotherapeutic agent-mediated cell cycle arrest. Gene profiling and bioinformatic analyses indicated that ectopic expression of miR-99a significantly upregulated genes that are critical for LSC maintenance, cell cycle, and downstream targets of E2F and MYC. This study suggests that miR-99a has a novel role and potential use as a biomarker in myeloid leukemia progression. PMID:27801668

  14. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia.

    PubMed

    Mavrakis, Konstantinos J; Wolfe, Andrew L; Oricchio, Elisa; Palomero, Teresa; de Keersmaecker, Kim; McJunkin, Katherine; Zuber, Johannes; James, Taneisha; Khan, Aly A; Leslie, Christina S; Parker, Joel S; Paddison, Patrick J; Tam, Wayne; Ferrando, Adolfo; Wendel, Hans-Guido

    2010-04-01

    MicroRNAs (miRNAs) have emerged as novel cancer genes. In particular, the miR-17-92 cluster, containing six individual miRNAs, is highly expressed in haematopoietic cancers and promotes lymphomagenesis in vivo. Clinical use of these findings hinges on isolating the oncogenic activity within the 17-92 cluster and defining its relevant target genes. Here we show that miR-19 is sufficient to promote leukaemogenesis in Notch1-induced T-cell acute lymphoblastic leukaemia (T-ALL) in vivo. In concord with the pathogenic importance of this interaction in T-ALL, we report a novel translocation that targets the 17-92 cluster and coincides with a second rearrangement that activates Notch1. To identify the miR-19 targets responsible for its oncogenic action, we conducted a large-scale short hairpin RNA screen for genes whose knockdown can phenocopy miR-19. Strikingly, the results of this screen were enriched for miR-19 target genes, and include Bim (Bcl2L11), AMP-activated kinase (Prkaa1) and the phosphatases Pten and PP2A (Ppp2r5e). Hence, an unbiased, functional genomics approach reveals a coordinate clampdown on several regulators of phosphatidylinositol-3-OH kinase-related survival signals by the leukaemogenic miR-19.

  15. miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

    PubMed Central

    Liu, Zixing; Smith, Kelly R.; Khong, Hung T.; Huang, Jingshan; Ahn, Eun-Young Erin; Zhou, Ming; Tan, Ming

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population. We identified that A20 (TNFAIP3) is a direct target of miR-125b in T cells. Overexpression of miR-125b also increased glucose uptake and oxygen consumption in T cells through targeting A20. Furthermore, restoration of A20 in miR-125b-overexpressing cells decreased the CD4-negative population in T cell leukemia, and decreased glucose uptake and oxygen consumption to the basal level of T cells transfected with vector. In conclusion, our data demonstrate that miR-125b regulates differentiation and reprogramming of T cell glucose metabolism via targeting A20. Since both de-differentiation and dysregulated glucose metabolism contribute to the development of T-cell leukemia, these findings provide novel insights into the understanding and treatment of T-ALL. PMID:27637078

  16. 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.

  17. A traditional Korean multiple herbal formulae (Yuk-Mi-Jihwang-Tang) attenuates acute restraint stress-induced brain tissue oxidation.

    PubMed

    Choi, Hyoung-Il; Lee, Hye-Won; Eom, Tae-Min; Lim, Sung-Ah; Ha, Hun-Yong; Seol, In-Chan; Kim, Yoon-Sik; Oh, Dal-Seok; Yoo, Ho-Ryong

    2017-04-01

    We aimed to evaluate the protective effects of Yuk-Mi-Jihwang-Tang (YJT) against acute restraint stress-induced brain oxidative damage. A water extract of YJT was prepared and subjected to high performance liquid chromatography - diode array detector-mass spectrometry (HPLC-DAD-MS). Thirty-six heads of C57BL/6J male mice (7 weeks) were divided into six groups (n = 6/group). The mice were orally administrated YJT (0, 50, 100, or 200 mg/kg) or vitamin C (100 mg/kg) for 5 consecutive days before 6 h of acute restraint stress. In the brain tissue, lipidperoxidation, antioxidant components, and pro-inflammatory cytokines were measured, and the serum corticosterone level was determined. Acute restraint stress-induced notably increased lipid peroxidation in brain tissues, and pretreatment with YJT showed a significant decreased the lipid peroxidation levels (p< 0.05). The levels of antioxidant components including total glutathione contents, activities of SOD and catalase were remarkably depleted by acute restraint stress, whereas these alterations were significantly restored by treatment with YJT (p< 0.05 or p< 0.01). The restraint stress markedly increased pro-inflammatory cytokines, such as TNF-α and IL-6 in the gene expression and protein levels (p< 0.05 or p< 0.01). Pretreatment with YJT significantly attenuated serum corticosterone (200 mg/kg, p < 0.05). YJT drastically attenuated the levels of 4- HNE, HO-1, Nox 2 and iNOSwhich were elevated during acute restraint stress, whereas the Nrf2 level was increased in brain tissue protein levels. Our data suggest that YJT protects the brain tissue against oxidative damage and regulates stress hormones.

  18. Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: A novel epigenetic-targeting approach in acute myeloid leukemia

    PubMed Central

    Mims, Alice; Walker, Alison R.; Huang, Xiaomeng; Sun, Jin; Wang, Hongyan; Santhanam, Ramasamy; Dorrance, Adrienne M.; Walker, Chris; Hoellerbauer, Pia; Tarighat, Somayeh S.; Chan, Kenneth K.; Klisovic, Rebecca B.; Perrotti, Danilo; Caligiuri, Michael A.; Byrd, John C.; Chen, Ching-Shih; Lee, L. James; Jacob, Samson; Mrózek, Krzysztof; Bloomfield, Clara D.; Blum, William; Garzon, Ramiro; Schwind, Sebastian; Marcucci, Guido

    2013-01-01

    Histone deacetylase (HDAC) inhibitors either alone or in combination with hypomethylating agents have limited clinical effect in acute myeloid leukemia (AML). Previously we demonstrated that AML patients with higher miR-29b expression had better response to the hypomethylating agent decitabine. Therefore, an increase in miR-29b expression preceding decitabine treatment may provide a therapeutic advantage. We previously showed that miR-29b expression is suppressed by a repressor complex that includes HDACs. Thus, HDAC inhibition may increase miR-29b expression. We hypothesized that priming AML cells with the novel HDAC inhibitor (HDACI) AR-42 would result in increased response to decitabine treatment via upregulation of miR-29b. Here we show that AR-42 is a potent HDACI in AML, increasing miR-29b levels and leading to downregulation of known miR-29b targets (i.e., SP1, DNMT1, DNMT3A, and DNMT3B). We then demonstrated that the sequential administration of AR-42 followed by decitabine resulted in a stronger anti-leukemic activity in vitro and in vivo than decitabine followed by AR-42 or either drug alone. These preclinical results with AR-42 priming before decitabine administration represents a promising, novel treatment approach and a paradigm shift with regard to the combination of epigenetic-targeting compounds in AML, where decitabine has been traditionally given before HDAC inhibitors. PMID:23178755

  19. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia.

    PubMed

    Mansour, Marc R; Sanda, Takaomi; Lawton, Lee N; Li, Xiaoyu; Kreslavsky, Taras; Novina, Carl D; Brand, Marjorie; Gutierrez, Alejandro; Kelliher, Michelle A; Jamieson, Catriona H M; von Boehmer, Harald; Young, Richard A; Look, A Thomas

    2013-07-29

    The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases of human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL in mouse models. By performing global microRNA (miRNA) expression profiling after depletion of TAL1, together with genome-wide analysis of TAL1 occupancy by chromatin immunoprecipitation coupled to massively parallel DNA sequencing, we identified the miRNA genes directly controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. The most dynamically regulated miRNA was miR-223, which is bound at its promoter and up-regulated by the TAL1 complex. miR-223 expression mirrors TAL1 levels during thymic development, with high expression in early thymocytes and marked down-regulation after the double-negative-2 stage of maturation. We demonstrate that aberrant miR-223 up-regulation by TAL1 is important for optimal growth of TAL1-positive T-ALL cells and that sustained expression of miR-223 partially rescues T-ALL cells after TAL1 knockdown. Overexpression of miR-223 also leads to marked down-regulation of FBXW7 protein expression, whereas knockdown of TAL1 leads to up-regulation of FBXW7 protein levels, with a marked reduction of its substrates MYC, MYB, NOTCH1, and CYCLIN E. We conclude that TAL1-mediated up-regulation of miR-223 promotes the malignant phenotype in T-ALL through repression of the FBXW7 tumor suppressor.

  20. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway

    PubMed Central

    Horie, Takahiro; Ono, Koh; Nishi, Hitoo; Nagao, Kazuya; Kinoshita, Minako; Watanabe, Shin; Kuwabara, Yasuhide; Nakashima, Yasuhiro; Takanabe-Mori, Rieko; Nishi, Eiichiro; Hasegawa, Koji; Kita, Toru; Kimura, Takeshi

    2010-01-01

    Aims A significant increase in congestive heart failure (CHF) was reported when the anti-ErbB2 antibody trastuzumab was used in combination with the chemotherapy drug doxorubicin (Dox). The aim of the present study was to investigate the role(s) of miRNAs in acute Dox-induced cardiotoxicity. Methods and results Neuregulin-1-ErbB signalling is essential for maintaining adult cardiac function. We found a significant reduction in ErbB4 expression in the hearts of mice after Dox treatment. Because the proteasome pathway was only partially involved in the reduction of ErbB4 expression, we examined the involvement of microRNAs (miRs) in the reduction of ErbB4 expression. miR-146a was shown to be up-regulated by Dox in neonatal rat cardiac myocytes. Using a luciferase reporter assay and overexpression of miR-146a, we confirmed that miR-146a targets the ErbB4 3′UTR. After Dox treatment, overexpression of miR-146a, as well as that of siRNA against ErbB4, induced cell death in cardiomyocytes. Re-expression of ErbB4 in miR-146a-overexpressing cardiomyocytes ameliorated Dox-induced cell death. To examine the loss of miR-146a function, we constructed ‘decoy’ genes that had tandem complementary sequences for miR-146a in the 3′UTR of a luciferase gene. When miR-146a ‘decoy’ genes were introduced into cardiomyocytes, ErbB4 expression was up-regulated and Dox-induced cell death was reduced. Conclusion These findings suggested that the up-regulation of miR-146a after Dox treatment is involved in acute Dox-induced cardiotoxicity by targeting ErbB4. Inhibition of both ErbB2 and ErbB4 signalling may be one of the reasons why those patients who receive concurrent therapy with Dox and trastuzumab suffer from CHF. PMID:20495188

  1. Evaluation of the miRNA profiling and effectiveness of the propolis on B-cell acute lymphoblastic leukemia cell line.

    PubMed

    Yilmaz, Ugur Cem; Bagca, Bakiye Goker; Karaca, Emin; Durmaz, Asude; Durmaz, Burak; Aykut, Ayca; Kayalar, Husniye; Avci, Cigir Biray; Susluer, Sunde Yilmaz; Gunduz, Cumhur; Cogulu, Ozgur

    2016-12-01

    Acute lymphoblastic leukemia (ALL) is one of the most frequent causes of death from cancer. Since the discovery of chemotherapeutic agents, ALL has become a model for improvement of survival. In parallel to this, serious side effects were observed and new natural therapeutic options has been discussed. One of these substances is called propolis which is a resinous substance gathered by honeybees. In the molecular era, miRNAs have been shown to play crucial roles in the development of many clinical conditions. The aim of this study is to evaluate the effect of Aydın propolis on 81 human miRNA activity in CCRF-SB leukemia cell line. Apoptotic effects of propolis on cell lines were also evaluated and apoptosis were found to be induced 1.5 fold in B-cell leukemia cells. The expression of 63 miRNAs (46 miRNAs were downregulated, 19 miRNAs were upregulated) in propolis treated leukemia cells have changed significantly (p<0.05). In conclusion propolis has changed expression of miRNAs which have epigenetic effects on leukemic cells. It is thought that it can be a promising agent for ALL treatment for future studies.

  2. The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA

    PubMed Central

    Masciarelli, Silvia; Larivera, Simone; Legnini, Ivano; Iosue, Ilaria; Bozzoni, Irene; Fazi, Francesco; Fatica, Alessandro

    2016-01-01

    Alterations in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia (AML) cells. Here, we identify the host transcript of miR-223, linc-223, as a novel functional long non-coding RNA (lncRNA) in AML. We show that from the primary nuclear transcript, the alternative production of miR-223 and linc-223 is finely regulated during monocytic differentiation. Moreover, linc-223 expression inhibits cell cycle progression and promotes monocytic differentiation of AML cells. We also demonstrate that endogenous linc-223 localizes in the cytoplasm and acts as a competing endogenous RNA for miR-125-5p, an oncogenic microRNA in leukemia. In particular, we show that linc-223 directly binds to miR-125-5p and that its knockdown increases the repressing activity of miR-125-5p resulting in the downregulation of its target interferon regulatory factor 4 (IRF4), which it was previously shown to inhibit the oncogenic activity of miR-125-5p in vivo. Furthermore, data from primary AML samples show significant downregulation of linc-223 in different AML subtypes. Therein, these findings indicate that the newly identified lncRNA linc-223 may have an important role in myeloid differentiation and leukemogenesis, at least in part, by cross-talking with IRF4 mRNA. PMID:27517498

  3. Detection of Acute Radiation Sickness: A Feasibility Study in Non-Human Primates Circulating miRNAs for Triage in Radiological Events

    PubMed Central

    Menon, Naresh; Rogers, Claude J.; Lukaszewicz, Agnes I.; Axtelle, James; Yadav, Marshleen; Song, Feifei; Chakravarti, Arnab; Jacob, Naduparambil K.

    2016-01-01

    Development of biomarkers capable of estimating absorbed dose is critical for effective triage of affected individuals after radiological events. Levels of cell-free circulating miRNAs in plasma were compared for dose-response analysis in non-human primates (NHP) exposed to lethal (6.5 Gy) and sub-lethal (1 and 3 Gy) doses over a 7 day period. The doses and test time points were selected to mimic triage needs in the event of a mass casualty radiological event. Changes in miRNA abundance in irradiated animals were compared to a non-irradiated cohort and a cohort experiencing acute inflammation response from exposure to lipopolysaccharide (LPS). An amplification-free, hybridization-based direct digital counting method was used for evaluation of changes in microRNAs in plasma from all animals. Consistent with previous murine studies, circulating levels of miR-150-5p exhibited a dose- and time-dependent decrease in plasma. Furthermore, plasma miR-150-5p levels were found to correlate well with lymphocyte and neutrophil depletion kinetics. Additionally, plasma levels of several other evolutionarily and functionally conserved miRNAs were found altered as a function of dose and time. Interestingly, miR-574-5p exhibited a distinct, dose-dependent increase 24 h post irradiation in NHPs with lethal versus sub-lethal exposure before returning to the baseline level by day 3. This particular miRNA response was not detected in previous murine studies but was observed in animals exposed to LPS, indicating distinct molecular and inflammatory responses. Furthermore, an increase in low-abundant miR-126, miR-144, and miR-21 as well as high-abundant miR-1-3p and miR-206 was observed in irradiated animals on day 3 and/or day 7. The data from this study could be used to develop a multi-marker panel with known tissue-specific origin that could be used for developing rapid assays for dose assessment and evaluation of radiation injury on multiple organs. Furthermore this approach may be

  4. Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways

    PubMed Central

    Ge, Qin-Min; Huang, Chun-Mei; Zhu, Xiang-Yang; Bian, Fan; Pan, Shu-Ming

    2017-01-01

    Objective To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways. Methods The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR. Results qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction. Conclusion This study

  5. Akt2 deficiency protects from acute lung injury via alternative macrophage activation and miR-146a induction in mice.

    PubMed

    Vergadi, Eleni; Vaporidi, Katerina; Theodorakis, Emmanuel E; Doxaki, Christina; Lagoudaki, Eleni; Ieronymaki, Eleftheria; Alexaki, Vassilia I; Helms, Mike; Kondili, Eumorfia; Soennichsen, Birte; Stathopoulos, Efstathios N; Margioris, Andrew N; Georgopoulos, Dimitrios; Tsatsanis, Christos

    2014-01-01

    Acute respiratory distress syndrome (ARDS) is a major cause of respiratory failure, with limited effective treatments available. Alveolar macrophages participate in the pathogenesis of ARDS. To investigate the role of macrophage activation in aseptic lung injury and identify molecular mediators with therapeutic potential, lung injury was induced in wild-type (WT) and Akt2(-/-) mice by hydrochloric acid aspiration. Acid-induced lung injury in WT mice was characterized by decreased lung compliance and increased protein and cytokine concentration in bronchoalveolar lavage fluid. Alveolar macrophages acquired a classical activation (M1) phenotype. Acid-induced lung injury was less severe in Akt2(-/-) mice compared with WT mice. Alveolar macrophages from acid-injured Akt2(-/-) mice demonstrated the alternative activation phenotype (M2). Although M2 polarization suppressed aseptic lung injury, it resulted in increased lung bacterial load when Akt2(-/-) mice were infected with Pseudomonas aeruginosa. miR-146a, an anti-inflammatory microRNA targeting TLR4 signaling, was induced during the late phase of lung injury in WT mice, whereas it was increased early in Akt2(-/-) mice. Indeed, miR-146a overexpression in WT macrophages suppressed LPS-induced inducible NO synthase (iNOS) and promoted M2 polarization, whereas miR-146a inhibition in Akt2(-/-) macrophages restored iNOS expression. Furthermore, miR-146a delivery or Akt2 silencing in WT mice exposed to acid resulted in suppression of iNOS in alveolar macrophages. In conclusion, Akt2 suppression and miR-146a induction promote the M2 macrophage phenotype, resulting in amelioration of acid-induced lung injury. In vivo modulation of macrophage phenotype through Akt2 or miR-146a could provide a potential therapeutic approach for aseptic ARDS; however, it may be deleterious in septic ARDS because of impaired bacterial clearance.

  6. Differential expression of the microRNAs in superior and inferior spikelets in rice (Oryza sativa).

    PubMed

    Peng, Ting; Lv, Qiang; Zhang, Jing; Li, Junzhou; Du, Yanxiu; Zhao, Quanzhi

    2011-10-01

    MicroRNAs (miRNAs) play a critical role in post-transcriptional gene regulation and have been shown to control many genes involved in various biological and metabolic processes. This work investigated miRNAs in rice (Oryza sativa), an important food crop. High-throughput sequencing technology was used to reveal expression differences in miRNAs between superior and inferior spikelets in rice (japonica cultivar Xinfeng 2) at 18 d after fertilization. Totals of 351 and 312 known miRNAs were obtained from the superior and inferior spikelets, respectively. Analysis of the expression profiles of these miRNAs showed that 189 miRNAs were differentially expressed between superior spikelets and inferior spikelets. In addition, 43 novel miRNAs were identified mostly by the accumulation of miRNA*s expressed differentially between the superior and inferior spikelets. Further analysis with bioinformatics software and comparison with existing databases showed that these differentially expressed miRNAs may individually participate in regulating hormone metabolism, carbohydrate metabolic pathways, and cell division during rice grain development. The results indicate that the slow grain-filling and low grain weight of rice inferior spikelets are attributed partly to differences in expression and function between superior and inferior spikelet miRNAs.

  7. 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.

  8. Effectiveness of milk whey protein-based ready-to-use therapeutic food in treatment of severe acute malnutrition in Malawian under-5 children: a randomised, double-blind, controlled non-inferiority clinical trial.

    PubMed

    Bahwere, Paluku; Banda, Theresa; Sadler, Kate; Nyirenda, Gertrude; Owino, Victor; Shaba, Bina; Dibari, Filippo; Collins, Steve

    2014-07-01

    The cost of ready-to-use therapeutic food (RUTF) used in community-based management of acute malnutrition has been a major obstacle to the scale up of this important child survival strategy. The current standard recipe for RUTF [peanut-based RUTF (P-RUTF)] is made from peanut paste, milk powder, oil, sugar, and minerals and vitamins. Milk powder forms about 30% of the ingredients and may represent over half the cost of the final product. The quality of whey protein concentrates 34% (WPC34) is similar to that of dried skimmed milk (DSM) used in the standard recipe and can be 25-33% cheaper. This blinded, parallel group, randomised, controlled non-inferiority clinical trial tested the effectiveness in treating severe acute malnutrition (SAM) of a new RUTF formulation WPC-RUTF in which WPC34 was used to replace DSM. Average weight gain (non-inferiority margin Δ = -1.2 g kg(-1) day(-1) ) and recovery rate (Δ = -10%) were the primary outcomes, and length of stay (LOS) was the secondary outcome (Δ = +14 days). Both per-protocol (PP) and intention-to-treat (ITT) analyses showed that WPC-RUTF was not inferior to P-RUTF for recovery rate [difference and its 95% confidence interval (CI) of 0.5% (95% CI -2.7, 3.7) in PP analysis and 0.6% (95% CI -5.2, 6.3) in ITT analysis] for average weight gain [0.2 (-0.5; 0.9) for both analyses] and LOS [-1.6 days (95% CI, -4.6, 1.4 days) in PP analysis and -1.9 days (95% CI, -4.6, 0.8 days) for ITT analysis]. In conclusion, whey protein-based RUTF is an effective cheaper alternative to the standard milk-based RUTF for the treatment of SAM.

  9. 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

  10. 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.

  11. Dissection of the major hematopoietic quantitative trait locus in chromosome 6q23.3 identifies miR-3662 as a novel player in hematopoiesis and acute myeloid leukemia

    PubMed Central

    Maharry, Sophia E.; Walker, Christopher J.; Liyanarachchi, Sandya; Mehta, Sujay; Patel, Mitra; Bainazar, Maryam A.; Huang, Xiaomeng; Lankenau, Malori A.; Hoag, Kevin W.; Ranganathan, Parvathi; Garzon, Ramiro; Blachly, James S.; Guttridge, Denis C.; Bloomfield, Clara D.; de la Chapelle, Albert; Eisfeld, Ann-Kathrin

    2016-01-01

    Chromosomal aberrations and multiple genome-wide association studies (GWASs) have established a major hematopoietic quantitative trait locus in chromosome 6q23.3. The locus comprises an active enhancer region, in which some of the associated SNPs alter transcription factor binding. We now identify microRNA-3662 as a new functional driver contributing to the associated phenotypes. The GWAS SNPs are strongly associated with higher miR-3662 expression. Genome editing of rs66650371, a three base pair deletion, suggests a functional link between the SNP genotype and the abundance of miR-3662. Increasing miR-3662’s abundance increases colony formation in hematopoietic progenitor cells, particularly the erythroid lineage. In contrast, miR-3662 is not expressed in acute myeloid leukemia cells and its overexpression has potent anti-leukemic effects in vitro and in vivo. Mechanistically, miR-3662 directly targets NF-ĸB-mediated transcription. Thus, miR-3662 is a new player of the hematopoietic 6q23.3 locus. PMID:27354268

  12. Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia

    PubMed Central

    2013-01-01

    Background Activating mutations [internal tandem duplication (ITD)] or overexpression of the FMS-like tyrosine kinase receptor-3 (FLT3) gene are associated with poor outcome in acute myeloid leukemia (AML) patients, underscoring the need for novel therapeutic approaches. The natural product silvestrol has potent antitumor activity in several malignancies, but its therapeutic impact on distinct molecular high-risk AML subsets remains to be fully investigated. We examined here the preclinical activity of silvestrol in FLT3-ITD and FLT3 wild-type (wt) AML. Methods Silvestrol in vitro anti-leukemic activity was examined by colorimetric cell viability assay, colony-forming and flow cytometry assays assessing growth inhibition and apoptosis, respectively. Pharmacological activity of silvestrol on FLT3 mRNA translation, mRNA and protein expression was determined by RNA-immunoprecipitation, qRT-PCR and immunoblot analyses, respectively. Silvestrol in vivo efficacy was investigated using MV4-11 leukemia-engrafted mice. Results Silvestrol shows antileukemia activity at nanomolar concentrations both in FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7 nM, respectively) and patients’ primary blasts [IC50 = ~12 nM (FLT3-wt) and ~5 nM (FLT3-ITD)]. Silvestrol increased apoptosis (~4fold, P = 0.0001), and inhibited colony-formation (100%, P < 0.0001) in primary blasts. Silvestrol efficiently inhibited FLT3 translation reducing FLT3 protein expression by 80–90% and decreased miR-155 levels (~60%), a frequently co-regulated onco-miR in FLT3-ITD-positive AML. The median survival of silvestrol-treated vs vehicle-treated mice was 63 vs 29 days post-engraftment, respectively (P < 0.0001). Conclusions Silvestrol exhibits significant in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of FLT3 and miR-155 expression. These encouraging results warrant a rapid

  13. Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

    PubMed Central

    Bousquet, Marina; Quelen, Cathy; Rosati, Roberto; Mansat-De Mas, Véronique; La Starza, Roberta; Bastard, Christian; Lippert, Eric; Talmant, Pascaline; Lafage-Pochitaloff, Marina; Leroux, Dominique; Gervais, Carine; Viguié, Franck; Lai, Jean-Luc; Terre, Christine; Beverlo, Berna; Sambani, Costantina; Hagemeijer, Anne; Marynen, Peter; Delsol, Georges; Dastugue, Nicole; Mecucci, Cristina; Brousset, Pierre

    2008-01-01

    Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity. PMID:18936236

  14. Platelet miRNAs and cardiovascular diseases.

    PubMed

    Fuentes, Eduardo; Palomo, Iván; Alarcón, Marcelo

    2015-07-15

    Activated platelets play a critical role in the acute complications of atherosclerosis that cause life-threatening ischemic events at late stages of the disease. The miRNAs are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. The miRNAs are known to be present in platelets and exert important regulatory functions. Here we systematically examine the genes that are regulated by platelet miRNAs (miRNA-223,miRNA-126,miRNA-21, miRNA-24 and miRNA-197) and the association with cardiovascular disease risks. Platelet-secreted miRNAs could be novel biomarkers associated with cardiovascular diseases.

  15. miR-153-3p, a new bio-target, is involved in the pathogenesis of acute graft-versus-host disease via inhibition of indoleamine- 2,3-dioxygenase

    PubMed Central

    Lv, Meng; Kong, Yuan; Luo, Hong-xue; Ye, Xiao-yang; Wu, Qi; Zhao, Tong-feng; Hu, Yue-huan; Zhang, Hong-yu; Huo, Ming-Rui; Wan, Jun; Huang, Xiao-jun

    2016-01-01

    Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Therefore, seeking reliable biomarkers and delineating the potential biological mechanism are important for optimizing treatment strategies and improving their curative effect. In this study, using a microRNA polymerase chain reaction (PCR)-based chip assay, microRNA-153-3p (miR-153-3p) was screened and selected as a potential biomarker of aGVHD. The elevated plasma miR-153-3p levels at +7 d after transplant could be used to predict the upcoming aGVHD. The area under the receiver operating characteristic curve for aGVHD+/aGVHD- patients receiving haploidentical transplant was 0.808 (95% confidence interval, 0.686-0.930) in a training set and 0.809 (95% confidence interval, 0.694-0.923) in a validation set. Interestingly, bioinformatics analysis indicated that indoleamine-2,3-dioxygenase (IDO) is a potential target of miR-153-3p. In vitro study confirmed that IDO could be directly inhibited by miR-153-3p. In a GVHD model, recipient mice injected with a miR-153-3p antagomir exhibited higher IDO expression levels at the early stage after transplantation, as well as delayed aGVHD and longer survival, indicating that the miR-153-3p level at +7 d post-transplant is a good predictor of aGVHD. miR-153-3p participates in aGVHD development by inhibiting IDO expression and might be a novel bio-target for aGVHD intervention. PMID:27340781

  16. 3,3’-Diindolylmethane attenuates LPS-mediated acute liver failure by regulating miRNAs to target IRAK4 and suppress Toll-like receptor signalling

    PubMed Central

    Tomar, S; Nagarkatti, M; Nagarkatti, P S

    2015-01-01

    Background and Purpose Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. 3,3′-Diindolylmethane (DIM) is a natural plant-derived compound with anti-cancer activities. Recently, DIM has also been shown to have anti-inflammatory properties. Here, we tested the hypothesis that DIM would suppress endotoxin-induced ALF. Experimental Approach We investigated the therapeutic potential of DIM in a mouse model of D-galactosamine/Lipopolysaccharide (GalN/LPS)-induced ALF. The efficacy of DIM treatment was assessed by survival, liver histopathology, serum levels of alanine transaminase, pro-inflammatory cytokines and number of activated liver macrophages. Effects of DIM on the expression of two miRNAs, 106a and 20b, and their predicted target gene were measured by qRT-PCR and Western blotting. Effects of DIM on the release of TNF-α from RAW264.7 macrophages transfected with mimics of these miRNAs and activated by LPS was assessed by elisa. Key Results DIM treatment protected mice from ALF symptoms and reduced the number of activated liver macrophages. DIM increased expression of miR-106a and miR-20b in liver mononuclear cells and decreased expression of their predicted target gene IL-1 receptor-associated kinase 4 (IRAK4), involved in signalling from Toll-like receptor 4 (TLR4). In vitro transfection of RAW264.7 cells using miRNA mimics of miR-106a and 20b decreased expression of IRAK4 and of TNF-α secretion, following LPS stimulation. Conclusions and Implications DIM attenuated GalN/LPS-induced ALF by regulating the expression of unique miRNAs that target key molecules in the TLR4 inflammatory pathway. DIM may represent a potential novel hepatoprotective agent. PMID:25521277

  17. Isolated inferior mesenteric portal hypertension with giant inferior mesenteric vein and anomalous inferior mesenteric vein insertion

    PubMed Central

    Prasad, G. Raghavendra; Billa, Srikar; Bhandari, Pavaneel; Hussain, Aijaz

    2013-01-01

    Extrahepatic portal hypertension is not an uncommon disease in childhood, but isolated inferior mesenteric portal varices and lower gastrointestinal (GI) bleed have not been reported till date. A 4-year-old girl presented with lower GI bleed. Surgical exploration revealed extrahepatic portal vein obstruction with giant inferior mesenteric vein and colonic varices. Inferior mesenteric vein was joining the superior mesenteric vein. The child was treated successfully with inferior mesenteric – inferior vena caval anastomosis. The child was relieved of GI bleed during the follow-up. PMID:23798814

  18. Electroacupuncture induces acute changes in cerebral cortical miRNA profile, improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke

    PubMed Central

    Zheng, Hai-zhen; Jiang, Wei; Zhao, Xiao-feng; Du, Jing; Liu, Pan-gong; Chang, Li-dan; Li, Wen-bo; Hu, Han-tong; Shi, Xue-min

    2016-01-01

    Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters miRNA expression in the cortex. In this study, we examined changes in the cerebral cortical miRNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong (GV26) and Neiguan (PC6), with a frequency of 2 Hz, continuous wave, current intensity of 3.0 mA, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. miRNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-miR-206-3p, rno-miR-3473, rno-miR-6216 and rno-miR-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated miRNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke. PMID:28197190

  19. 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

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

    PubMed

    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

    2016-03-01

    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.

  1. Fasa Registry on Acute Myocardial Infarction (FaRMI): Feasibility Study and Pilot Phase Results

    PubMed Central

    Askari, Alireza; Zakeri, Habib; Farjam, Mojtaba; Dehghan, Azizallah; Zendehdel, Kazem

    2016-01-01

    Background Myocardial infarction (MI) is the leading cause of death in Iran. Every attempt to improve treatment patterns and patient outcomes needs a surveillance system to both consider the efficacy and safety measures. Fasa Registry on Myocardial Infarction (FaRMI) is the first population-based registry for acute MI in Iran targeted to provide meticulous description of patients’ characteristics, to explore the management patterns of these patients, to discover the degree of adherence to the practice guidelines, and to investigate the determinants of poor in-hospital and later outcomes. Methods A diagnosis of acute MI (type I, II and III) was made upon the accepted criteria by the attending cardiologists and types IV and V MI were excluded. Two registrar nurses gathered data on demographics, place of residence and ethnicity, past medical history, risk factors, and the clinical course. Management patterns in the pre-hospital setting, during the hospital stay and at the discharge time were recorded. Routine laboratory results and cardiac biomarkers on three consecutive days were registered. Results pilot phase included the first 95 patients, 63.5% of whom were men and 31.5% were women. With a mean age of 62.89±13.75 years among participants, the rate of premature MI was 31.8%. ST segment elevation MI accounted for 68.2% cases and inferior wall was the most prevalent region involved followed by anterior and posterior walls. Discussion Obtained data on the characteristics of patients suffering an MI event revealed the major determinants of delay in initiation of therapies and contributors of poor outcome. Completeness of data was guaranteed upon involvement of multiple checkpoints and data quality was secured by means of automatic validation processes in addition to weekly physicians’ roundups. Conclusion Execution of FaRMI in the form presented is feasible and it will build up a comprehensive population-based registry for MI in the region. PMID:27907128

  2. 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.

  3. miR-125b and miR-100 Are Predictive Biomarkers of Response to Induction Chemotherapy in Osteosarcoma

    PubMed Central

    Kubota, Daisuke; Kosaka, Nobuyoshi; Yoshida, Akihiko; Arai, Yasuhito; Qiao, Zhiwei; Ochiya, Takahiro; Kawai, Akira

    2016-01-01

    Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear. We investigated miRNA expression in eight open biopsy samples to identify miRNAs predictive of response to induction chemotherapy and thus maybe used for risk stratification therapy. The samples were obtained from four patients with inferior necrosis (Huvos I/II) and four patients with superior necrosis (Huvos III/IV) following induction chemotherapy. We found six miRNAs, including miR-125b and miR-100, that were differentially expressed > 2-fold (p < 0.05) in patients who respond poorly to treatment. The association between poor prognosis and the abundance of miR-125b and miR-100 was confirmed by quantitative reverse transcriptase-polymerase chain reaction in 20 additional osteosarcoma patients. Accordingly, overexpression of miR-125b and miR-100 in three osteosarcoma cell lines enhanced cell proliferation, invasiveness, and resistance to chemotherapeutic drugs such as methotrexate, doxorubicin, and cisplatin. In addition, overexpression of miR-125b blocked the ability of these chemotherapy agents to induce apoptosis. As open biopsy is routinely performed to diagnose osteosarcoma, levels of miR-125b and miR-100 in these samples may be used as basis for risk stratification therapy. PMID:27990096

  4. Reprogramming of miRNA networks in cancer and leukemia.

    PubMed

    Volinia, Stefano; Galasso, Marco; Costinean, Stefan; Tagliavini, Luca; Gamberoni, Giacomo; Drusco, Alessandra; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Abu Jarour, Ramzey; Desponts, Caroline; Teitell, Michael; Baffa, Raffaele; Aqeilan, Rami; Iorio, Marilena V; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Catozzi, Marco; Previati, Maurizio; Ambs, Stefan; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Harris, Curtis C; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Rassenti, Laura Z; Kipps, Thomas J; Huebner, Kay; Pichiorri, Flavia; Lenze, Dido; Cairo, Stefano; Buendia, Marie-Annick; Pineau, Pascal; Dejean, Anne; Zanesi, Nicola; Rossi, Simona; Calin, George A; Liu, Chang-Gong; Palatini, Jeff; Negrini, Massimo; Vecchione, Andrea; Rosenberg, Anne; Croce, Carlo M

    2010-05-01

    We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network.

  5. Reprogramming of miRNA networks in cancer and leukemia

    PubMed Central

    Volinia, Stefano; Galasso, Marco; Costinean, Stefan; Tagliavini, Luca; Gamberoni, Giacomo; Drusco, Alessandra; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Abu Jarour, Ramzey; Desponts, Caroline; Teitell, Michael; Baffa, Raffaele; Aqeilan, Rami; Iorio, Marilena V.; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Catozzi, Marco; Previati, Maurizio; Ambs, Stefan; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Harris, Curtis C.; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Rassenti, Laura Z.; Kipps, Thomas J.; Huebner, Kay; Pichiorri, Flavia; Lenze, Dido; Cairo, Stefano; Buendia, Marie-Annick; Pineau, Pascal; Dejean, Anne; Zanesi, Nicola; Rossi, Simona; Calin, George A.; Liu, Chang-Gong; Palatini, Jeff; Negrini, Massimo; Vecchione, Andrea; Rosenberg, Anne; Croce, Carlo M.

    2010-01-01

    We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network. PMID:20439436

  6. 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...

  7. 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.

  8. 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"…

  9. MicroRNA miR-125b causes leukemia.

    PubMed

    Bousquet, Marina; Harris, Marian H; Zhou, Beiyan; Lodish, Harvey F

    2010-12-14

    MicroRNA miR-125b has been implicated in several kinds of leukemia. The chromosomal translocation t(2;11)(p21;q23) found in patients with myelodysplasia and acute myeloid leukemia leads to an overexpression of miR-125b of up to 90-fold normal. Moreover, miR-125b is also up-regulated in patients with B-cell acute lymphoblastic leukemia carrying the t(11;14)(q24;q32) translocation. To decipher the presumed oncogenic mechanism of miR-125b, we used transplantation experiments in mice. All mice transplanted with fetal liver cells ectopically expressing miR-125b showed an increase in white blood cell count, in particular in neutrophils and monocytes, associated with a macrocytic anemia. Among these mice, half died of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, or a myeloproliferative neoplasm, suggesting an important role for miR-125b in early hematopoiesis. Furthermore, coexpression of miR-125b and the BCR-ABL fusion gene in transplanted cells accelerated the development of leukemia in mice, compared with control mice expressing only BCR-ABL, suggesting that miR-125b confers a proliferative advantage to the leukemic cells. Thus, we show that overexpression of miR-125b is sufficient both to shorten the latency of BCR-ABL-induced leukemia and to independently induce leukemia in a mouse model.

  10. Panmedullary edema with inferior olivary hypertrophy in bilateral medial medullary infarction.

    PubMed

    Inoue, Yasuteru; Miyashita, Fumio; Koga, Masatoshi; Yamada, Naoaki; Toyoda, Kazunori; Minematsu, Kazuo

    2014-03-01

    Bilateral medial medullary infarction (MMI) is a rare type of stroke with poor outcomes. Inferior olivary nucleus hypertrophy results from a pathologic lesion in the Guillain-Mollaret triangle. The relationship between inferior olivary nucleus hypertrophy and the medullary lesion is obscure. To the best of our knowledge, only 1 autopsy case with unilateral medial medullary infarction that was associated with ipsilateral inferior olivary nucleus hypertrophy has been reported. We describe a rare case with acute infarction in the bilateral medial medulla oblongata accompanied by subacute bilateral inferior olivary nucleus hypertrophy and panmedullary edema. The hypertrophy appeared to have been caused by local ischemic damage to the termination of the central tegmental tract at the bilateral inferior olivary nucleus.

  11. 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

  12. Disappearance of myocardial bridging of the left anterior descending coronary artery after inferior myocardial infarction.

    PubMed

    Yıldız, Bekir Serhat; Esin, Fatma; Alihanoğlu, Yusuf Izzettin; Kılıç, Ismail Doğu; Evrengül, Harun

    2014-06-01

    Myocardial bridging (MB) is defined as the intramural course of a major epicardial coronary artery, and is mostly confined to the left ventricle and the left anterior descending coronary artery (LAD). MB is a common congenital abnormality of a coronary artery, and is usually thought to be a benign anatomical variant. Although rare, previous studies have reported that patients with MB may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias, and even sudden death. Therefore, the diagnosis and treatment of MB are both important. Since MB is congenital, its disappearance is unlikely. We here report a very rare case of disappearance of MB after inferior MI.

  13. Shape recognition and inferior temporal neurons.

    PubMed Central

    Schwartz, E L; Desimone, R; Albright, T D; Gross, C G

    1983-01-01

    Inferior temporal cortex plays an important role in shape recognition. To study the shape selectivity of single inferior temporal neurons, we recorded their responses to a set of shapes systematically varying in boundary curvature. Many inferior temporal neurons were selective for stimuli of specific boundary curvature and maintained this selectivity over changes in stimulus size or position. The method of describing boundary curvature was that of Fourier descriptors. PMID:6577453

  14. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis.

    PubMed

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher; Oral, Haluk Barbaros

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p < 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

  15. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

    PubMed Central

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p < 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis. PMID:27722176

  16. Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

    PubMed Central

    Koeth, Oliver; Zeymer, Uwe; Schiele, Rudolf; Zahn, Ralf

    2010-01-01

    Takotsubo cardiomyopathy (TCM) is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI) is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM. PMID:20811565

  17. 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.

  18. 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.

  19. 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

  20. Inferior hip dislocation after falling from height: A case report

    PubMed Central

    Tekin, Ali Çağrı; Çabuk, Haluk; Büyükkurt, Cem Dinçay; Dedeoğlu, Süleyman Semih; İmren, Yunus; Gürbüz, Hakan

    2016-01-01

    Introduction Traumatic inferior hip dislocation is the least common of all hip dislocations. Adult inferior hip dislocations usually occur after high-energy trauma, very few cases are reported without fracture. Presentation of case A 26-year-old female was brought to the emergency department with severe pain in the left hip, impaired posture and restricted movement following a fall from 15 m height. The hip joint was fixed in 90° flexion, 15° abduction, and 20° external rotation. No neurovascular impairment was determined. On radiologic examination, a left ischial type inferior hip dislocation was detected. Hemorrhagic shock which developed due to acute blood loss to thoracic and abdominal cavity and patient died at third hour after she was brought to the hospital. Discussion Traumatic hip dislocations have high morbidity and mortality rates due to multiple organ damage, primarily of the extremities, chest and abdomen. In the treatment of traumatic hip dislocation, closed reduction is recommended through muscle relaxation under general anesthesia or sedation. This procedure should be applied before any intervention for concomitant extremity injuries. A detailed evaluation on emergency presentation, a multi-disciplinary approach and early diagnosis with the rapid application of imaging methods could be life-saving for such patients. PMID:27058153

  1. 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

  2. Inferior alveolar nerve block: Alternative technique

    PubMed Central

    Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

    2012-01-01

    Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. Aim and Objective: The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. Materials and Methods: This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. Conclusion: This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages. PMID:25885503

  3. Bioinformatics facilitating the use of microarrays to delineate potential miRNA biomarkers in aristolochic acid nephropathy

    PubMed Central

    Chen, Xi; Lu, Haitao

    2016-01-01

    Aristolochic acid nephropathy (AAN) is a rapidly progressive acute or chronic tubulointerstitial nephritis (TIN). The present study attempted to explore the molecular mechanisms underlying the miRNA-directed development of AAN. Our differentially expressed analysis identified 11 DE-miRNAs and retrieved the target genes of these DE-miRNAs; then, network analysis and functional analysis further identified 6 DE-miRNAs (has-miR-192, has-miR-194, has-miR-542-3p, has-miR-450a, has-miR-584, has-miR-33a) as phenotypic biomarkers of AAN. Surprisingly, of has-miR-192 has been reported to be associated with the pathogenesis of AAN, and has-miR-194, has-miR-542-3p and has-miR-450a was first-time identified to link to the development of AAN. In addition, the expressional changes of has-miR-584 and has-miR-33a may be associated with the development of AAN as well, which must be further confirmed by the associated experiments. Taken together, our work reveals for the first time the regulatory mechanisms of miRNAs in the development of AAN and this will contribute to miRNA-based diagnosis and treatment of AAN. PMID:27418141

  4. [Inferior vestibular neuritis: diagnosis using VEMP].

    PubMed

    Walther, L E; Repik, I

    2012-02-01

    Vestibular evoked myogenic potentials (VEMP) are a new method to establish the functional status of the otolith organs. The sacculocollic reflex of the cervical VEMP to air conduction (AC) reflects predominantly saccular function due to saccular afferents to the inferior vestibular nerve. We describe a case of inferior vestibular neuritis as a rare differential diagnosis of vestibular neuritis. Clinical signs were a normal caloric response, unilaterally absent AC cVEMPs and bilaterally preserved ocular VEMPs (AC oVEMPs).

  5. miRNA expression is modulated over time after focal ischaemia: up-regulation of miR-347 promotes neuronal apoptosis.

    PubMed

    Gubern, Carme; Camós, Susanna; Ballesteros, Iván; Rodríguez, Rocío; Romera, Víctor G; Cañadas, Roberto; Lizasoain, Ignacio; Moro, María A; Serena, Joaquín; Mallolas, Judith; Castellanos, Mar

    2013-12-01

    Despite the large number of molecules reported as being over-expressed after ischaemia, little is known regarding their regulation. miRNAs are potent post-transcriptional regulators of gene expression, and reports have shown differentially miRNA expression in response to focal cerebral ischaemia. The present study analysed miRNA expression from acute to late phases of ischaemia to identify specific ischaemia-related miRNAs, elucidate their role, and identify potential targets involved in stroke pathophysiology. Of 112 miRNAs, 32 showed significant changes and different expression profiles. In addition to the previously reported differentially expressed miRNAs, new ischaemia-regulated miRNAs have been found, including miR-347. Forty-seven genes involved in brain functions or related to ischaemia are predicted to be potential targets of the differentially expressed miRNAs after middle cerebral artery occlusion. Analysis of four of these targets (Acsl4, Arf3, Btg2 and Dpysl5) showed them to be differentially regulated by ischaemia at the transcriptional or post-transcriptional level. Acsl4, Bnip3l and Phyhip, potential targets of miR-347, were up-regulated after miR-347 over-expression, inducing neuronal apoptotic death. Our findings suggest that miR-347 plays an important role in regulating neuronal cell death, identify Acsl4 as a new protein requiring study in ischaemia, and provide an important resource for future functional studies of miRNAs after ischaemia.

  6. 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

  7. 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

  8. Preservation of the recipient inferior vena cava in liver transplantation.

    PubMed

    Pereira, F; Herrera, J; Mora, N P; Nuño, J; Turrión, V S; Vicente, E; Ardaiz, J

    1994-01-01

    Twenty piggy-back (PB) liver transplantations (LT) were compared with 20 LT performed by the standard technique in order to evaluate whether or not the theoretical haemodynamic advantages of the preservation of the inferior vena cava (IVC) have any impact on the final results of the LT. Statistically significant differences were observed in the duration of the hepatectomy, which was longer for PB LT (192 min vs. 146 min), and in the duration of the anhepatic phase, which was shorter in that group (52 min vs. 76 min). There were no differences in the duration of the complete surgical procedure, consumption of blood products, incidence of postoperative acute renal failure, number of reoperations or survival.

  9. Catheter directed interventions for inferior vena cava thrombosis

    PubMed Central

    Warhit, Michael; Matsunaga, Felipe; Cynamon, Jacob

    2016-01-01

    Inferior vena cava (IVC) thrombosis, although similar in many aspects to deep venous thrombosis (DVT), has distinct clinical implications, treatments and roles for endovascular management. Etiologies of IVC thrombosis vary from congenital malformations of the IVC to acquired, where indwelling IVC filters have been implicated as a leading cause. With an increasing incidence of IVC thrombosis throughout the United States, clinicians need to be educated on the clinical signs and diagnostic tools available to aid in the diagnosis as well as available treatment options. Untreated IVC thrombus can result in serious morbidity and mortality, both in the acute phase with symptoms related to venous outflow occlusion and embolism, and in the long-term, sequelae of post-thrombotic syndrome (PTS) related to chronic venous occlusion. This manuscript will discuss the clinical presentation of IVC thrombosis, diagnostic and treatment options, as well as the role of endovascular management. PMID:28123981

  10. Inferior Vena Cava Filters for Recurrent Thrombosis

    PubMed Central

    Patel, Salil H.; Patel, Rima

    2007-01-01

    Inferior vena cava filters are often used as alternatives to anticoagulant therapy for the prevention of pulmonary embolism. Many of the clinical data that support the use of these devices stem from relatively limited retrospective studies. The dual purpose of this review is to examine the incidence of thrombotic complications associated with inferior vena cava filters and to discuss the role of anticoagulant therapy concurrent with filter placement. Device-associated morbidity and overall efficacy can be considered only in the context of rates of vena cava thrombosis, insertion-site thrombosis, recurrent deep venous thrombosis, and recurrent pulmonary embolism. PMID:17622366

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

    PubMed

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

    2015-04-01

    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.

  12. Efferent pathways modulate hyperactivity in inferior colliculus.

    PubMed

    Mulders, Wilhelmina Henrica A M; Seluakumaran, Kumar; Robertson, Donald

    2010-07-14

    Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.

  13. 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

  14. Leiomyosarcoma arising from the inferior mesenteric vein

    PubMed Central

    Clemente, Gennaro; Sarno, Gerardo; Barbaro, Brunella; Nuzzo, Gennaro

    2009-01-01

    Leyomiosarcomas arising from the portal/mesenteric venous system are very rare tumours, and only a few cases have been reported in the global literature. As the other leyomiosarcomas of vascular origin, they are associated with a poor prognosis. The present report describes the case of a 66-year-old woman with a leyomiosarcoma of the inferior mesenteric vein, unexpectedly found during a CT scan performed for another indication. A brief review of the literature is also given. The patient underwent radical surgical excision and enjoys a good health, without radiological signs of recurrence, 24 months after surgery. In this case, an early incidental diagnosis determined an early treatment and, probably, a favourable prognosis. This is the second case of leyomiosarcoma of the inferior mesenteric vein reported in the literature. PMID:21686492

  15. Leiomyosarcoma of the Inferior Vena Cava

    PubMed Central

    Sadri, Ben Abid; Amine, Attaoui Mohamed; Zeineb, Mzoughi; Nizar, Miloudi; Lassad, Gharbi; Khalfallah, Mohamed Tahar

    2013-01-01

    Vascular leiomyosarcoma (LMS) are unique. The inferior vena cava (IVC) is the most affected organ (about 38% cases). We report the observation of a 50-year old woman who consulted for right upper quadrant pain. Imaging studies revealed a retroperitoneal mass that mimic a LMS of the IVC. The patient was operated. A resection of the IVC along with the tumor was performed without reconstruction. The management of LMS is surgical and depends upon the location and tumor characteristics. PMID:24765501

  16. Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals

    PubMed Central

    Morris, Tim P; Fielding, Katherine; Carpenter, James R; Phillips, Patrick P J

    2016-01-01

    Objective To assess the adequacy of reporting of non-inferiority trials alongside the consistency and utility of current recommended analyses and guidelines. Design Review of randomised clinical trials that used a non-inferiority design published between January 2010 and May 2015 in medical journals that had an impact factor >10 (JAMA Internal Medicine, Archives Internal Medicine, PLOS Medicine, Annals of Internal Medicine, BMJ, JAMA, Lancet and New England Journal of Medicine). Data sources Ovid (MEDLINE). Methods We searched for non-inferiority trials and assessed the following: choice of non-inferiority margin and justification of margin; power and significance level for sample size; patient population used and how this was defined; any missing data methods used and assumptions declared and any sensitivity analyses used. Results A total of 168 trial publications were included. Most trials concluded non-inferiority (132; 79%). The non-inferiority margin was reported for 98% (164), but less than half reported any justification for the margin (77; 46%). While most chose two different analyses (91; 54%) the most common being intention-to-treat (ITT) or modified ITT and per-protocol, a large number of articles only chose to conduct and report one analysis (65; 39%), most commonly the ITT analysis. There was lack of clarity or inconsistency between the type I error rate and corresponding CIs for 73 (43%) articles. Missing data were rarely considered with (99; 59%) not declaring whether imputation techniques were used. Conclusions Reporting and conduct of non-inferiority trials is inconsistent and does not follow the recommendations in available statistical guidelines, which are not wholly consistent themselves. Authors should clearly describe the methods used and provide clear descriptions of and justifications for their design and primary analysis. Failure to do this risks misleading conclusions being drawn, with consequent effects on clinical practice. PMID:27855102

  17. 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.

  18. 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 ...

  19. 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 ...

  20. 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

    2016-02-08

    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.

  1. 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

  2. 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.

  3. Combining anti-miR-155 with chemotherapy for the treatment of lung cancers.

    PubMed

    Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro; Ivan, Cristina; Rodriguez-Aguayo, Cristian; Fuentes-Mattei, Enrique; Xiao, Lianchun; Vannini, Ivan; Redis, Roxana; D'Abundo, Lucilla; Zhang, Xinna; Nicoloso, Milena S; Rossi, Simona; Gonzalez-Villasana, Vianey; Rupaimoole, Rajesha; Ferracin, Manuela; Morabito, Fortunato; Neri, Antonino; Ruvolo, Peter; Ruvolo, Vivian R; Pecot, Chad V; Amadori, Dino; Aruzzo, Lynne; Calin, Steliana; Wang, Xuemei; You, M James; Ferrajoli, Alessandra; Orlowski, Robert Z; Plunkett, William; Lichtenberg, Tara; Davuluri, Ramana V; Berindan-Neagoe, Ioana; Negrini, Massimo; Wistuba, Ignacio I; Hagop, Kantarjian; Sood, Anil K; Lopez-Berestein, Gabriel; Keating, Michael J; Fabbri, Muller; Calin, George A

    2016-11-30

    Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia and acute lymphoblastic leukemia. Results We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that anti-miR-155-DOPC can be considered non-toxic in vivo. We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism, and demonstrate that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions Our findings support the existence of a miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death.

  4. 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

  5. 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

  6. Unusual case of left ventricular ballooning involving the inferior wall: a case report

    PubMed Central

    2009-01-01

    Background Tako – tsubo like syndrome (also named left ventricular apical ballooning) is an unusual cardiomyopathy with an high incidence in Japanese population of female sex, following an emotional stress. The clinical features (typical chest pain), and the electrocardiographic changes (negative T wave and persistent ST elevation in anterior leads), are suggestive of an acute myocardial infarction; nevertheless the coronary angiography show coronary arteries without lesions and the ventriculography show specific segmental dysfunction. In the literature there are many reports of typical left ventricular ballooning (apical); due to the rarity of the atypical localizations (such as mid, basal, anterior or inferior left ventricular wall) many authors think they are different physiopatologic entity. Case report We report a case of 50 – years old woman, with a family history of ischeamic cardiomyopathy but with no additional cardiovascular risk factors, who arrived to emergency department with a recent episode of chest pain (about 30 minutes) with electrocardiographic and echocardiographic features suggested of a inferior ST elevation myocardial infarction. Coronary angiography showed coronary arteries without atherosclerotic lesions; ventriculography showed an inferior dysfunction. Conclusion This data can suggest for an atypical form (in term of clinical presentation and localization) of left ventricular ballooning involving the inferior wall (never described in the literature), not preceded by any emotional or physical stress. The follow – up performed by transthoracic echocardiography (2 months later) revealed a complete regression of wall motions abnormalities. PMID:19232097

  7. Complete heart block in late presentation of inferior STEMI successfully treated with percutaneous coronary intervention.

    PubMed

    Liang, Michael; Chin, John; Pasupati, Sanjeevan

    2011-09-01

    A 55-year-old female presented with 4-day history of fatigue and exertional shortness of breath. A late presentation inferior ST elevation myocardial infarction (STEMI) was diagnosed based on ST elevation in the inferior leads of electrocardiography and elevated cardiac troponin T (TnT). She developed complete heart block 1 day after admission to the hospital and remained hemodynamically stable. She was taken to the catheterization laboratory for a temporary pacing wire insertion. Coronary angiogram at the same time showed an occluded right coronary artery at the mid-section. The lesion was successfully opened. Within 24 hours, the patient's heart rhythm returned to sinus with first-degree atrioventricular block (AVB), thus avoiding the need for a permanent pacemaker. Current guidelines recommend medical management for late presentation hemodynamically stable STEMI of more than 72 H onset. Current ACC/AHA/HRS Pacemaker Guidelines recommend reperfusion strategy for acute presentation inferior STEMI associated with AVB. However, no clear strategy exists in the case of late presentation inferior STEMI with advanced AVB. Our case report suggests that late coronary intervention could be a management strategy in such a scenario in order to avoid a permanent pacemaker.

  8. Decompression of inferior alveolar nerve: case report.

    PubMed

    Marques, Tiago Miguel Santos; Gomes, Joana Marques

    2011-01-01

    Paresthesia as a result of mechanical trauma is one of the most frequent sensory disturbances of the inferior alveolar nerve. This case report describes surgical treatment for paresthesia caused by a compressive phenomenon within the mandibular canal. The cause of the compression, a broken instrument left in the patient's mouth during previous endodontic therapy, was identified during routine radiography and computed tomography. Once the foreign object was removed by surgery, the paresthesia resolved quickly. This case highlights the potential for an iatrogenic mechanical cause of paresthesia.

  9. Predictive value of the fragmented QRS complex in 6-month mortality and morbidity following acute coronary syndrome

    PubMed Central

    Akbarzadeh, Fariborz; Pourafkari, Leili; Ghaffari, Samad; Hashemi, Mohammad; Sadeghi-Bazargani, Homayoun

    2013-01-01

    Background Fragmented QRS encompasses different RSR’ patterns showing various morphologies of the QRS complexes with or without the Q wave on a resting 12-lead electrocardiogram. It has been shown possibly to cause adverse cardiac outcomes in patients with some heart diseases, including coronary artery disease. In view of the need for risk stratification of patients presenting with acute coronary syndrome in the most efficacious and cost-effective way, we conducted this study to clarify the value of developing fragmented QRS in a cohort of patients presenting with their first acute coronary syndrome in predicting 6-month mortality and morbidity. Methods One hundred consecutive patients admitted to the coronary care unit at Shahid Madani Heart Center in Tabriz from December 2008 to March 2009 with their first acute coronary syndrome were enrolled in this prospective study. Demographic and electrocardiographic data on admission, inhospital mortality, and need for revascularization were recorded. Electrocardiography performed 2 months after the index event was examined for development of fragmented QRS. Mortality and morbidity was evaluated at 6-month follow-up in all patients. Results The patients were of mean age 57.7 ± 12.8 years, and 84% were men. The primary diagnosis was unstable angina in 17 (17%) patients, non-ST elevation myocardial infarction (MI) in 11 (11%), anterior or inferior ST elevation MI in 66 (66%), and postero-inferior MI in six (6%). Fragmented QRS was present in 30 (30%) patients during the first admission, which increased to 44% at the 2-month follow-up and to 53% at the 6-month follow-up. The presence of various coronary risk factors and drug therapy given, including fibrinolytic agents, had no effect on development of fragmented QRS. Mortality was significantly higher (P = 0.032) and left ventricular ejection fraction was significantly lower (P = 0.001) in the fragmented QRS group at the 6-month follow-up. Conclusion This study strongly

  10. 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.

  11. Heart block and cardiac embolization of fractured inferior vena cava filter

    PubMed Central

    Abudayyeh, Islam; Takruri, Yessar; Weiner, Justin B

    2016-01-01

    Objective: A 66-year-old man underwent a placement of an inferior vena cava filter before a gastric surgery 9 years prior, presented to the emergency room with a complete atrioventricular block. Chest x-ray and transthoracic echocardiogram showed struts migrating to right ventricle with tricuspid regurgitation. Cardiothoracic surgery was consulted and declined an open surgical intervention due to the location of the embolized fragments and the patient’s overall condition. It was also felt that the fragments had migrated chronically and were adhered to the cardiac structures. Methods: The patient underwent a dual-chamber permanent pacemaker implantation. Post-implant fluoroscopy showed no displacement of the inferior vena cava filter struts due to the pacemaker leads indicating that the filter fracture had likely been a chronic process. Results: This case highlights a rare combination of complications related to inferior vena cava filter fractures and the importance of assessing for such fractures in chronic placements. Inferior vena cava filter placement for a duration greater than 1 month can be associated with filter fractures and strut migration which may lead to, although rare, serious or fatal complications such as complete atrioventricular conduction system disruption and valvular damage including significant tricuspid regurgitation. Conclusions: Assessing for inferior vena cava filter fractures in chronic filter placement is important to avoid such complications. When possible, retrieval of the filter should be considered in all patients outside the acute setting in order to avoid filter-related complications. Filter retrieval rates remain low even when a retrievable filter is in place and the patient no longer has a contraindication to anticoagulation. PMID:28228959

  12. Chronic ethanol feeding alters miRNA expression dynamics during liver regeneration

    PubMed Central

    Dippold, Rachael P.; Vadigepalli, Rajanikanth; Gonye, Gregory E.; Patra, Biswanath; Hoek, Jan B.

    2012-01-01

    Background Adaptation to chronic ethanol treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease. Methods In this study we investigated the effect of chronic ethanol intake on hepatic miRNA expression in male Sprague-Dawley rats during the initial 24 hrs of liver regeneration following 70% partial hepatectomy (PHx) using microRNA (miRNA) microarrays. miRNA expression during adaptation to ethanol was investigated using RT-qPCR. Nuclear Factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation. Results Unsupervised clustering of miRNA expression profiles suggested that miRNA expression was more affected by chronic ethanol feeding than by the acute challenge of liver regeneration after PHx. Several miRNAs that were significantly altered by chronic ethanol feeding, including miRs-34a, -103, -107, and -122 have been reported to play a role in regulating hepatic metabolism and the onset of these miRNA changes occurred gradually during the time course of ethanol feeding. Chronic ethanol feeding also altered the dynamic miRNA profile during liver regeneration. Promoter analysis predicted a role for Nuclear Factor kappa B (NFκB) in the immediate early miRNA response to PHx. NFκB binding at target miRNA promoters in the chronic ethanol-fed group was significantly altered and these changes directly correlated with the observed expression dynamics of the target miRNA. Conclusions Chronic ethanol consumption alters the hepatic miRNA expression profile such that the response of the metabolism-associated miRNAs occurs during long-term adaptation to ethanol rather than as an acute transient response to ethanol metabolism. Additionally, the dynamic miRNA program during liver regeneration in response to PHx is altered in the chronically ethanol-fed liver and these differences reflect, in part, differences

  13. Analysis of the miRNA profile in C6/36 cells persistently infected with dengue virus type 2.

    PubMed

    Avila-Bonilla, Rodolfo Gamaliel; Yocupicio-Monroy, Martha; Marchat, Laurence A; De Nova-Ocampo, Mónica A; Del Ángel, Rosa María; Salas-Benito, Juan Santiago

    2017-03-15

    Dengue virus (DENV) is the most important arbovirus in the world; DENV is transmitted by the Aedes genus of mosquitoes and can establish a life-long persistent infection in mosquitoes. However, the exact mechanism by which persistent infection is established remains unknown. In this study the differential expression of miRNAs was analysed by deep sequencing and RT-qPCR using a previously established C6/36-HT cell line persistently infected with DENV 2 (C6-L) as a model. miR-927, miR-87, miR-210, miR-2a-3p, miR-190 and miR-970 were up-regulated, whereas miR-252, miR-263a-3p, miR-92b, miR-10-5p miR-9a-5p, miR-9a-1, miR-124, miR-286a and miR-286b were down-regulated in C6-L cells compared with C6/36 cells acutely infected with the same virus or mock-infected cells. Deep sequencing results were validated by RT-qPCR for the highly differentially expressed miR-927 and miR-9a-5p, which were up- and down-regulated, respectively, compared with both acutely and mock-infected C6/36 cells. The putative targets of these miRNAs include components of the ubiquitin conjugation pathway, vesicle-mediated transport, autophagy, and the JAK-STAT cascade as well as proteins with endopeptidase activity. Other putative targets include members of the Toll signalling pathway and proteins with kinase, ATPase, protease, scavenger receptor or Lectin C-type activity or that participate in fatty acid biosynthesis or oxidative stress. Our results suggest that several specific miRNAs help regulate the cellular functions that maintain equilibrium between viral replication and the antiviral response during persistent infection of mosquito cells. This study is the first report of a global miRNA profile in a mosquito cell line persistently infected with DENV.

  14. CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

    PubMed Central

    Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P

    2015-01-01

    Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675

  15. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction

    PubMed Central

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Éric; Gaudreault, Valérie

    2014-01-01

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause. PMID:25276306

  16. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

    PubMed

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie

    2014-09-26

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  17. Partial breast reconstruction with mini superficial inferior epigastric artery and mini deep inferior epigastric perforator flaps.

    PubMed

    Spiegel, Aldona J; Eldor, Liron

    2010-08-01

    In this study, partial breast reconstruction was undertaken after breast conservation therapy using mini abdominal free flaps on both an immediate and delayed basis.Patient demographics, oncologic status, reconstructive data, and complications were collected from medical records.Twelve patients (age range 39-60) were included in this study with a mean follow-up time of 5 years. Ten mini superficial inferior epigastric artery flaps and 2 mini deep inferior epigastric perforator flaps were used (7 immediate and 5 delayed reconstructions). No flap lost, 1 minor abdominal wound dehiscence, and no local or distant recurrences were noted. Good to excellent results were reported by 91% of the women.In properly selected patients with high motivation toward breast conservation, tailored abdominal mini-free flaps can safely and satisfactorily be implemented for the reconstruction of partial mastectomy defects. Patients should be comprehensively educated on the potential future implications of using the abdominal donor site for partial breast reconstruction.

  18. 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

  19. Uses of the Inferior Oblique Muscle in Strabismus Surgery

    PubMed Central

    Stager, David; Dao, Lori M.; Felius, Joost

    2015-01-01

    Inferior oblique muscle weakening is typically performed for overaction of the muscle. In this article, we review inferior oblique muscle anatomy, different weakening procedures, and recent surgical techniques that take advantage of the muscle's unique anatomy for the treatment of additional indications such as excyclotorsion and hypertropia in primary gaze. PMID:26180466

  20. 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.

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

    PubMed Central

    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.

    2015-01-01

    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

  2. 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.

  3. Complications of inferior vena cava filters

    PubMed Central

    Grewal, Simer; Chamarthy, Murthy R.

    2016-01-01

    Inferior vena cava (IVC) filter placement is a relatively low risk alternative for prophylaxis against pulmonary embolism in patients with pelvic or lower extremity deep venous thrombosis who are not suitable for anticoagulation. There is an increasing trend in the number of IVC filter implantation procedures performed every year. There are many device types in the market and in the early 2000s, the introduction of retrievable filters brought an additional subset of complications to consider. Modern filter designs have led to decreased morbidity and mortality, however, a thorough understanding of the limitations and complications of IVC filters is necessary to weight the risks and benefits of placing IVC filters. In this review, the complications associated with IVC filters are divided into procedure related, post-procedure, and retrieval complications. Differences amongst the device types and retrievable filters are described, though this is limited by a significant lack of prospective studies. Additionally, the clinical presentation as well as prevention and treatment strategies are outlined with each complication type. PMID:28123983

  4. MiR-181b Antagonizes Atherosclerotic Plaque Vulnerability Through Modulating Macrophage Polarization by Directly Targeting Notch1.

    PubMed

    An, Tian-Hui; He, Quan-Wei; Xia, Yuan-Peng; Chen, Sheng-Cai; Baral, Suraj; Mao, Ling; Jin, Hui-Juan; Li, Ya-Nan; Wang, Meng-Die; Chen, Jian-Guo; Zhu, Ling-Qiang; Hu, Bo

    2016-10-08

    Atherosclerotic plaque vulnerability is the major cause for acute stroke and could be regulated by macrophage polarization. MicroRNA-181b (miR-181b) was involved in macrophage differential. Here, we explore whether miR-181b could regulate atherosclerotic plaque vulnerability by modulating macrophage polarization and the underline mechanisms. In acute stroke patients with atherosclerotic plaque, we found that the serum level of miR-181b was decreased. Eight-week apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into three groups (N = 10): mice fed with normal saline (Ctrl), mice fed with high-fat diet, and tail vein injection with miRNA agomir negative control (AG-NC)/miR-181b agomir (181b-AG, a synthetic miR-181b agonist). We found that the serum level of miR-181b in AG-NC group was lower than that in Ctrl group. Moreover, 181b-AG could upregulate miR-181b expression, reduce artery burden and attenuate atherosclerotic plaque vulnerability by modulating macrophage polarization. In RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL), we found miR-181b could reverse the function of ox-LDL on M1/M2 markers at both mRNA and protein levels. Furthermore, by employing luciferase reporter assay, we found that Notch1 was a direct target of miR-181b and could be regulated by miR-181b in vivo and in vitro. Finally, inhibition of Notch1 could abolish the function of downregulating miR-181b on increasing M2 phenotype macrophages. Our study demonstrates that administration of miR-181b could reduce atherosclerotic plaque vulnerability partially through modulating macrophage phenotype by directly targeting Notch1.

  5. Study of the <mi>Zc>+ channel using lattice QCD

    SciTech Connect

    Prelovsek, Sasa; Lang, C. B.; Leskovec, Luka; Mohler, Daniel

    2015-01-01

    Recently experimentalists have discovered several charged charmoniumlike hadrons mi>Zmi>mi>cmi>+ with unconventional quark content mi>c>¯mi>c>mi>d>¯mi>u>. We perform a search for mi>Zmi>mi>cmi>+ with mass below 4.2 GeV in the channel mi>Imi>mi>G>(mi>Jmi>mi>Pmi>mi>C>)=1+(1+-) using lattice QCD. The major challenge is presented by the two-meson states mi>Jmi>/mi>ψmi>π>, mi>ψ>2mi>Smi>mi>π>, mi>ψ>1mi>Dmi>

  6. 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

  7. Progressive limb ataxia following inferior olive lesions

    PubMed Central

    Horn, K M; Deep, A; Gibson, A R

    2013-01-01

    Cerebellar climbing fibres originate in the inferior olive (IO). Temporary IO inactivation produces movement deficits. Does permanent inactivation produce similar deficits and, if so, do they recover? The excitotoxin, kainic acid, was injected into the rostral IO of three cats. Behaviour was measured during reaching and locomotion. Two cats were injected during the reaching task. Within minutes, grasping became difficult and the trajectories of the reaches showed higher arcing than normally seen. During locomotion, both cats showed head and trunk deviation to the injected side, walking paths curved to the injected side, and the paws were lifted higher than normal. Limbs contralateral to the injections became rigid. Within 1 day, posture had normalized, locomotion was unsteady and high lifting of the paws had reversed to a tendency to drag the dorsum of the paws. Passive body movement produced vestibular signs. Over a few days, locomotion normalized and vestibular signs disappeared. Reach trajectories were normal but grasping deficits persisted. Over the first week, the amplitude of limb lift during reaching and locomotion began to increase. The increase continued over time and, after several months, limb movements became severely ataxic. The effects followed the somatotopy of the rostral IO: a loss of cells in medial rostral IO only affected the forelimb, whereas a loss of cells in medial and lateral IO affected both forelimb and hindlimb. Deficits produced by IO lesions involve multiple mechanisms; some recover rapidly, some appear stable, and some worsen over time. The nature of the progressive deficit suggests a gradual loss of Purkinje cell inhibition on cerebellar nuclear cells. PMID:23027819

  8. miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways

    PubMed Central

    Fang, Zhi Hong; Wang, Si Li; Zhao, Jin Tao; Lin, Zhi Juan; Chen, Lin Yan; Su, Rui; Xie, Si Ting; Carter, Bing Z; Xu, Bing

    2016-01-01

    MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission. Restoration of miR-150 markedly inhibited growth and induced apoptosis of leukemia cells, and reduced tumorigenicity in a xenograft leukemia murine model. Microarray analysis identified multiple novel targets of miR-150, which were validated by quantitative real-time PCR and luciferase reporter assay. Gene ontology and pathway analysis illustrated potential roles of these targets in small-molecule metabolism, transcriptional regulation, RNA metabolism, proteoglycan synthesis in cancer, mTOR signaling pathway, or Wnt signaling pathway. Interestingly, knockdown one of four miR-150 targets (EIF4B, FOXO4B, PRKCA, and TET3) showed an antileukemia activity similar to that of miR-150 restoration. Collectively, our study demonstrates that miR-150 functions as a tumor suppressor through multiple mechanisms in human leukemia and provides a rationale for utilizing miR-150 as a novel therapeutic agent for leukemia treatment. PMID:27899822

  9. [Combined resection of liver and inferior vena cava].

    PubMed

    Sherba, A E; Efimov, D Iu; Rummo, O O

    2014-01-01

    It was analyzed the results of treatment of 8 patients. Combined resection of liver and inferior vena cava was done in all cases. All resections of inferior vena cava were performed in combination with right-sided hemihepatectomy. Circular resection of inferior vena cava was done in 6 cases, tangential-in 2 cases. Allograft of donor inferior vena cava was used in 3 cases for reconstruction of inferior vena cava. Average duration of combined resection of liver and inferior vena cava was 675±189 min, average hemorrhage - 1800±1402 ml. The need for transfusion of packed red blood cells was 270±723 ml, the need for transfusion of fresh frozen plasma was 1105±636 ml. Post-resection liver failure according to criteria ISGLS developed in 3 patients (37.5%). Biliary complications such as biliary fistula and inconsistency of hepatico-jejunal anastomosis developed in 2 patients (25%). Hospital mortality was 12.5%. It is considered that resection of liver with inferior vena cava demands an experience in hepatobiliary surgery and/or liver transplantation. Surgeon must be ready to use total vascular isolation, hypothermic preservation and veno-venous bypass grafting. It allows to dilate an opportunity of resection liver surgery.

  10. 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

  11. Acute myocardial infarction in a young man using anabolic steroids.

    PubMed

    Wysoczanski, Mariusz; Rachko, Maurice; Bergmann, Steven R

    2008-01-01

    Anabolic-androgenic steroids are used worldwide to help athletes gain muscle mass and strength. Their use and abuse is associated with numerous side effects, including acute myocardial infarction (MI). We report a case of MI in a young 31-year-old bodybuilder. Because of the serious cardiovascular complications of anabolic steroids, physicians should be aware of their abuse and consequences.

  12. Acute ST-segment elevation myocardial infarction: The prognostic importance of lead augmented vector right and leads V7–V9

    PubMed Central

    Hebbal, Veeresh Patil; Setty, Huliyurdurga Srinivasasetty Natraj; Sathvik, Cholenahalli Manjunath; Patil, Vikram; Sahoo, Sarthak; Manjunath, Cholenahalli Nanjappa

    2017-01-01

    Background: Acute myocardial infarction (MI) is associated with high mortality and among survivors have high morbidity. Electrocardiogram (ECG), a cost-effective and easily available, has traditionally been used not only just for diagnosis of MI but also for culprit vessel recognition and for prognostication. However, the role of lead augmented vector right (aVR) and leads V7–V9 in acute MI are often neglected in clinical practice. We studied the role of lead aVR and leads V7–V9 in ST-elevation MI (STEMI) patients. Methods: A total of 209 patients presenting with STEMI were enrolled in the study. History of comorbid conditions and habits was enquired. Routine blood tests were performed. Full spectrum ECG (including V7–9) and 2D-ECHO was performed on all patients. All the patients underwent revascularization by primary percutaneous coronary intervention. The role of lead aVR, lead V7, and leads V8–9 was analyzed in anterior wall MI (AWMI) and inferior wall MI. All the patients were followed up for 1 month for outcome assessment. Results: Of the 209 patients, 85.1% were males and 35.8% were diabetic, 60.2% were smokers, AWMI accounted for 55.5%. Lead aVR ST deviation was noted in 75.1% of patients (elevation in 17.7% and depression in 47.1%). V7 ST elevation occurred in 27.6% and V8–9 elevation occurred in 7.5% of the study population. Total death was 11.9% in the study (including the in-hospital mortality), all these patients had lead aVR ST segment deviation (P < 0.001). Conclusion: Lead aVR ST deviation and Lead V7 ST deviation helps to prognosticate the STEMI patients as high risk and those with aVR ST depression had higher mortality compared to aVR ST elevation because of larger myocardial involvement. PMID:28250684

  13. <mi>J/ψ> production at low transverse momentum in <mi>p+p> and <mi>d> + Au collisions at <mi>smi><mi>Nmi>N>=200 GeV

    SciTech Connect

    Adamczyk, L.

    2016-06-10

    In this paper, we report on the measurement of J/ψ production in the dielectron channel at midrapidity (|y| < 1) in p + p and d + Au collisions at <mi>smi><mi>Nmi>N>=200 from the STAR experiment at the Relativistic Heavy Ion Collider. The transverse momentum pT spectra in p + p for pT < 4 GeV/c and d + Au collisions for pT < 3 GeV/c are presented. These measurements extend the STAR coverage for J/ψ production in p + p collisions to low pT . The < p$2\\atop{T}$ > from the measured J/ψ invariant cross section in p + p and d + Au collisions are evaluated and compared to similar measurements at other collision energies. The nuclear modification factor for J/ψ is extracted as a function of pT and collision centrality in d + Au and compared to model calculations using the modified nuclear parton distribution function and a final-state J/ψ nuclear absorption cross section.

  14. 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.

  15. [Congenital anomalies of the inferior vena cava: role of imaging].

    PubMed

    Manfredi, R; Cotroneo, A R; Pirronti, T; Macis, G; Marano, P

    1995-10-01

    In recent years, clinics and radiology of congenital anomalies of the inferior vena cava have increased in importance in planning abdominal surgery, liver or kidney transplantation, or new interventional or diagnostic procedures such as the positioning of inferior vena cava filters to prevent pulmonary embolism, varicocel sclerotherapy and renal venous sampling. In the past, the radiologic assessment of these rare anomalies was performed only with angiography, which remains the most accurate diagnostic method. Today, besides angiography, less invasive examinations can be performed, e.g., US, CT and MRI, with MRA. In the last two years, 5 patients with inferior vena cava anomalies were examined: 3 had double inferior vena cava and 2 azygos continuation. All of them were submitted to US, CT, MRI and MRA and 3 patients underwent also angiography, two of them with double puncture. US can suggest the diagnosis but may be limited by technical factors and in the assessment of the whole inferior vena cava. Enhanced CT can depict anomaly extent, but uses contrast agents and ionizing radiations. Angiography better depicts craniocaudal spread and collateral networks but is an invasive procedure and sometimes needs a double puncture (double inferior vena cava). MRI, with MRA, yields the same information as the other modalities, but without contrast agents or ionizing radiations. The development of velocity encoded sequences will probably make this technique the method of choice in the study of inferior vena cava anomalies. Our study was aimed at reviewing the embryo-genesis of inferior vena cava anomalies and to assess the relative importance of different diagnostic procedures in the diagnosis and staging of these anomalies.

  16. Auditory scene analysis following unilateral inferior colliculus infarct.

    PubMed

    Champoux, François; Paiement, Philippe; Vannasing, Phetsamone; Mercier, Claude; Gagné, Jean-Pierre; Lepore, Franco; Lassonde, Maryse

    2007-11-19

    Event-related potentials in the form of mismatch negativity were recorded to investigate auditory scene analysis capabilities in a person with a very circumscribed haemorrhagic lesion at the level of the right inferior colliculus. The results provide the first objective evidence that processing at the level of the inferior colliculus plays an important role in human auditory frequency discrimination. Moreover, the electrophysiological data suggest that following this unilateral lesion, the auditory pathways fail to reorganize efficiently.

  17. Glucose utilization in the inferior cerebellar vermis and ocular myoclonus.

    PubMed

    Yakushiji, Y; Otsubo, R; Hayashi, T; Fukuchi, K; Yamada, N; Hasegawa, Y; Minematsu, K

    2006-07-11

    In a patient with symptomatic ocular myoclonus, the authors observed the regional cerebral metabolic rate of glucose use (rCMRGlu) before and after successful treatment with clonazepam. Even after the symptoms resolved, the rCMRGlu in the hypertrophic olive increased persistently, whereas that in the inferior cerebellar vermis contralateral to the hypertrophic olive decreased. The inferior cerebellar vermis, belonging to the vestibulocerebellar system, may be associated with the generation of symptomatic ocular myoclonus.

  18. miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway

    PubMed Central

    Xu, Dan-dan; Zhou, Peng-jun; Wang, Ying; Zhang, Yi; Zhang, Rong; Zhang, Li; Chen, Su-hong; Fu, Wu-yu; Ruan, Bi-bo; Xu, Hai-peng; Hu, Chao-zhi; Tian, Lu; Qin, Jin-hong; Wang, Sheng; Wang, Xiao; Liu, Qiu-ying; Ren, Zhe; Gu, Xue-kui; Li, Yao-he; Liu, Zhong; Wang, Yi-fei

    2016-01-01

    Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs) plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs; CD34+CD38- cells). miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples. Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro. Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumor growth. Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level. Moreover, luciferase reporter assays indicated Nanog is a direct and functional target of miR-150. Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects. Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1. These results provide insights into the specific biological behavior of miR-150 in regulating LSC proliferation and tumorigenicity. Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia. PMID:27917123

  19. Inferior ectopic pupil and typical ocular coloboma in RCS rats.

    PubMed

    Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

    2011-08-01

    Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

  20. Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

    PubMed

    Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

    2014-04-01

    Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct.

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

    PubMed

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

    2016-01-06

    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.

  2. Anterior transposition of the inferior oblique muscle as the initial treatment of a snapped inferior rectus muscle.

    PubMed

    Aguirre-Aquino, B I; Riemann, C D; Lewis, H; Traboulsi, E I

    2001-02-01

    Snapping or tearing of an extraocular muscle refers to its rupture across its width, usually at the junction between muscle and tendon several millimeters behind the insertion. Tearing occurs during strabismus or retinal reattachment surgery, or after trauma. If the proximal end of the muscle cannot be located, transposition procedures are necessary to achieve ocular realignment. These surgical procedures carry the risk of anterior segment ischemia, especially in the elderly. Anterior transposition of the inferior oblique muscle has been used for the treatment of inferior oblique overaction, especially in the presence of a dissociated vertical deviation, and in patients with fourth nerve palsy. We transposed the inferior oblique muscle insertion in a 73-year-old woman with a snapped inferior rectus muscle.

  3. 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

  4. 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.

  5. Switching of adenosine diphosphate receptor inhibitor after hospital discharge among myocardial infarction patients: Insights from the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study.

    PubMed

    Zettler, Marjorie E; Peterson, Eric D; McCoy, Lisa A; Effron, Mark B; Anstrom, Kevin J; Henry, Timothy D; Baker, Brian A; Messenger, John C; Cohen, David J; Wang, Tracy Y

    2017-01-01

    The reasons for postdischarge adenosine diphosphate receptor inhibitor (ADPri) switching among patients with myocardial infarction (MI) are unclear. We sought to describe the incidence and patterns of postdischarge ADPri switching among patients with acute MI treated with percutaneous coronary intervention.

  6. Circulating inflammatory miRNA signature in response to different doses of aerobic exercise.

    PubMed

    de Gonzalo-Calvo, David; Dávalos, Alberto; Montero, Ana; García-González, Ángela; Tyshkovska, Iryna; González-Medina, Antonio; Soares, Sara M A; Martínez-Camblor, Pablo; Casas-Agustench, Patricia; Rabadán, Manuel; Díaz-Martínez, Ángel E; Úbeda, Natalia; Iglesias-Gutiérrez, Eduardo

    2015-07-15

    While moderate acute exercise has been associated with strong anti-inflammatory mechanisms, strenuous exercise has been linked to deleterious inflammatory perturbations. It is therefore fundamental to elucidate the mechanisms that regulate the exercise-induced inflammatory cascade. Information on novel regulators such as circulating inflammatory microRNAs (c-inflammamiRs) is incomplete. In this study, we evaluated the response of a panel of c-inflammamiRs to different doses of acute aerobic exercise. We first studied the exercise-induced inflammatory cascade in serum samples of nine active middle-aged males immediately before and after (0 h, 24 h, 72 h) 10-km, half-marathon, and marathon races. Next, we analyzed the circulating profile of 106 specific c-inflammamiRs immediately before) and after (0 h, 24 h) 10-km (low inflammatory response) and marathon (high inflammatory response) races. Analysis of classical inflammatory parameters revealed a dose-dependent effect of aerobic exercise on systemic inflammation, with higher levels detected after marathon. We observed an increase in miR-150-5p immediately after the 10-km race. Levels of 12 c-inflammamiRs were increased immediately after the marathon (let-7d-3p, let-7f-2-3p, miR-125b-5p, miR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p, miR-29a-3p, miR-34a-5p, miR-424-3p, and miR-424-5p). c-inflammamiRs returned to basal levels after 24 h. Correlation and in silico analyses supported a close association between the observed c-inflammamiR pattern and regulation of the inflammatory process. In conclusion, we found that different doses of acute aerobic exercise induced a distinct and specific c-inflammamiR response, which may be associated with control of the exercise-induced inflammatory cascade. Our findings point to c-inflammamiRs as potential biomarkers of exercise-induced inflammation, and hence, exercise dose.

  7. 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.

  8. Inferior oblique muscle paresis as a sign of myasthenia gravis.

    PubMed

    Almog, Yehoshua; Ben-David, Merav; Nemet, Arie Y

    2016-03-01

    Myasthenia gravis may affect any of the six extra-ocular muscles, masquerading as any type of ocular motor pathology. The frequency of involvement of each muscle is not well established in the medical literature. This study was designed to determine whether a specific muscle or combination of muscles tends to be predominantly affected. This retrospective review included 30 patients with a clinical diagnosis of myasthenia gravis who had extra-ocular muscle involvement with diplopia at presentation. The diagnosis was confirmed by at least one of the following tests: Tensilon test, acetylcholine receptor antibodies, thymoma on chest CT scan, or suggestive electromyography. Frequency of involvement of each muscle in this cohort was inferior oblique 19 (63.3%), lateral rectus nine (30%), superior rectus four (13.3%), inferior rectus six (20%), medial rectus four (13.3%), and superior oblique three (10%). The inferior oblique was involved more often than any other muscle (p<0.01). Eighteen (60%) patients had ptosis, six (20%) of whom had bilateral ptosis. Diagnosing myasthenia gravis can be difficult, because the disease may mimic every pupil-sparing pattern of ocular misalignment. In addition diplopia caused by paresis of the inferior oblique muscle is rarely encountered (other than as a part of oculomotor nerve palsy). Hence, when a patient presents with vertical diplopia resulting from an isolated inferior oblique palsy, myasthenic etiology should be highly suspected.

  9. 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.

  10. 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

    2016-06-01

    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.

  11. Changes in the Expression of miR-34a and its Target Genes Following Spinal Cord Injury In Rats

    PubMed Central

    Chen, Ying; Cao, Shuyan; Xu, Pingping; Han, Wei; Shan, Tiankai; Pan, Jingying; Lin, Weiwei; Chen, Xue; Wang, Xiaodong

    2016-01-01

    Background Results from DNA microarray experiments have shown that the expression of miR-34s undergoes significant changes following spinal cord injury (SCI). The present study was designed to detect changes in the expression of miR-34s and its target genes during the acute and sub-acute stages of SCI. Material/Methods Luxol fast blue (LFB) staining for myelin was used to observe the differences in the general morphology of the spinal cord after SCI in a contusion model in rats. qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI. The mimic technique was used to further confirm the regulatory effect of miR-34a on the potential target genes. Results The expression level of miR-34a decreased immediately after SCI and persisted for 21 days after SCI. The expression level of miR-34c began decreasing at day 1 after SCI and persisted until day 14. The expression level of miR-34b did not undergo significant change after SCI. The results of double immunofluorescence and in-situ hybridization suggested that miR-34a was highly expressed in spinal cord neurons. Based on our bioinformatics analysis, we postulated that miR-34a might participate in post-SCI cell apoptosis by regulating the target gene Notch1, and likely participated in the inflammatory response and glial scar formation by regulating the candidate genes Csf1r and PDGFRα, respectively. The expression levels of the candidate genes Csf1r and PDGFRα were consistent with Notch1 after SCI. The mimic technique further confirmed the regulatory effect of miR-34a on the aforementioned target genes. Conclusions We postulate that miR-34a and miR-34c might participate in multiple aspects of cytobiological activities following SCI. MiR-34a in particular may participate in cell apoptosis, inflammatory response, and glial scar formation by regulating the target gene Notch1 and candidate target genes Csf1r and PDGFRα respectively. PMID:27780189

  12. 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.

  13. 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.

  14. Identification of miRNAs and miRNA-mediated regulatory pathways in Carica papaya.

    PubMed

    Liang, Gang; Li, Yang; He, Hua; Wang, Fang; Yu, Diqiu

    2013-10-01

    Plant microRNAs (miRNAs) post-transcriptionally regulate target gene expression to modulate growth and development and biotic and abiotic stress responses. By analyzing small RNA deep sequencing data in combination with the genome sequence, we identified 75 conserved miRNAs and 11 novel miRNAs. Their target genes were also predicted. For most conserved miRNAs, the miRNA-target pairs were conserved across plant species. In addition to these conserved miRNA-target pairs, we also identified some papaya-specific miRNA-target regulatory pathways. Both miR168 and miR530 target the Argonaute 1 gene, indicating a second autoregulatory mechanism for miRNA regulation. A non-conserved miRNA was mapped within an intron of Dicer-like 1 (DCL1), suggesting a conserved homeostatic autoregulatory mechanism for DCL1 expression. A 21-nt miRNA triggers secondary siRNA production from its target genes, nucleotide-binding site leucine-rich repeat protein genes. Certain phased-miRNAs were processed from their conserved miRNA precursors, indicating a putative miRNA evolution mechanism. In addition, we identified a Carica papaya-specific miRNA that targets an ethylene receptor gene, implying its function in the ethylene signaling pathway. This work will also advance our understanding of miRNA functions and evolution in plants.

  15. 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

    2015-12-26

    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.

  16. The History of Primary Angioplasty and Stenting for Acute Myocardial Infarction.

    PubMed

    Smilowitz, Nathaniel R; Feit, Frederick

    2016-01-01

    The evolution of the management of acute myocardial infarction (MI) has been one of the crowning achievements of modern medicine. At the turn of the twentieth century, MI was an often-fatal condition. Prolonged bed rest served as the principal treatment modality. Over the past century, insights into the pathophysiology of MI revolutionized approaches to management, with the sequential use of surgical coronary artery revascularization, thrombolytic therapy, and percutaneous coronary intervention (PCI) with primary coronary angioplasty, and placement of intracoronary stents. The benefits of prompt revascularization inspired systems of care to provide rapid access to PCI. This review provides a historical context for our current approach to primary PCI for acute MI.

  17. Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.

    PubMed

    Wang, Wen; Liu, Zhi; Su, Jie; Chen, Wen-Sheng; Wang, Xiao-Wu; Bai, San-Xing; Zhang, Jin-Zhou; Yu, Shi-Qiang

    2016-08-01

    Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.

  18. 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.

  19. Variant Inferior Alveolar Nerves and Implications for Local Anesthesia

    PubMed Central

    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

  20. Information conveyed by inferior colliculus neurons about stimuli with aligned and misaligned sound localization cues

    PubMed Central

    Young, Eric D.

    2011-01-01

    Previous studies have demonstrated that single neurons in the central nucleus of the inferior colliculus (ICC) are sensitive to multiple sound localization cues. We investigated the hypothesis that ICC neurons are specialized to encode multiple sound localization cues that are aligned in space (as would naturally occur from a single broadband sound source). Sound localization cues including interaural time differences (ITDs), interaural level differences (ILDs), and spectral shapes (SSs) were measured in a marmoset monkey. Virtual space methods were used to generate stimuli with aligned and misaligned combinations of cues while recording in the ICC of the same monkey. Mutual information (MI) between spike rates and stimuli for aligned versus misaligned cues were compared. Neurons with best frequencies (BFs) less than ∼11 kHz mostly encoded information about a single sound localization cue, ITD or ILD depending on frequency, consistent with the dominance of ear acoustics by either ITD or ILD at those frequencies. Most neurons with BFs >11 kHz encoded information about multiple sound localization cues, usually ILD and SS, and were sensitive to their alignment. In some neurons MI between stimuli and spike responses was greater for aligned cues, while in others it was greater for misaligned cues. If SS cues were shifted to lower frequencies in the virtual space stimuli, a similar result was found for neurons with BFs <11 kHz, showing that the cue interaction reflects the spectra of the stimuli and not a specialization for representing SS cues. In general the results show that ICC neurons are sensitive to multiple localization cues if they are simultaneously present in the frequency response area of the neuron. However, the representation is diffuse in that there is not a specialization in the ICC for encoding aligned sound localization cues. PMID:21653729

  1. 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

  2. Facial palsy after inferior alveolar nerve block: case report and review of the literature.

    PubMed

    Chevalier, V; Arbab-Chirani, R; Tea, S H; Roux, M

    2010-11-01

    Bell's palsy is an idiopathic and acute, peripheral nerve palsy resulting in inability to control facial muscles on the affected side because of the involvement of the facial nerve. This study describes a case of Bell's palsy that developed after dental anaesthesia. A 34-year-old pregnant woman at 35 weeks of amenorrhea, with no history of systemic disease, was referred by her dentist for treatment of a mandibular left molar in pulpitis. An inferior alveolar nerve block was made prior to the access cavity preparation. 2h later, the patient felt the onset of a complete paralysis of the left-sided facial muscles. The medical history, the physical examination and the complementary exams led neurologists to the diagnosis of Bell's palsy. The treatment and results of the 1-year follow-up are presented and discussed. Bell's palsy is a rare complication of maxillofacial surgery or dental procedures, the mechanisms of which remain uncertain.

  3. The Development of Hypertrophic Inferior Olivary Nucleus in Oculopalatal Tremor.

    PubMed

    Jun, Bokkwan

    2016-12-01

    Oculopalatal tremor is an acquired clinical condition resulting from the interruption of the dentato-rubro-olivary neuronal pathway. The signal change in inferior olivary nucleus and its hypertrophy on magnetic resonance imaging (MRI) can be observed prior to the development of symptomatic oculopalatal tremor. This is a case of the fourth cranial nerve palsy followed by oculopalatal tremor, and increased signal intensity in inferior olivary nucleus on MRI was observed in 7 months after damage to the dentate-rubro-olivary pathway and 5 months prior to the development of oscillopsia and oculopalatal tremor.

  4. MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

    PubMed

    Bostjancic, E; Zidar, N; Stajner, D; Glavac, D

    2010-01-01

    MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

  5. Acute myocardial infarction with concomitant pulmonary embolism as a result of patent foramen ovale.

    PubMed

    Hayıroğlu, Mert İlker; Bozbeyoğlu, Emrah; Akyüz, Şükrü; Yıldırımtürk, Özlem; Bozbay, Mehmet; Bakhshaliyev, Nijad; Renda, Emir; Gök, Gülay; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-07-01

    Acute myocardial infarction (MI) and pulmonary embolism canal one lead to life-threatening conditions such as sudden cardiac death and congestive heart failure. We discuss a case of a 74-year-old man presented to the emergency department with acute dyspnea and chest pain. Acute anterior MI and pulmonary embolism concomitantly were diagnosed. Primary percutaneous coronary intervention performed because of preliminary acute anterior MI diagnosis. Transthoracic echocardiography was performed to determine further complications caused by acute MI because patient had a continuous tachycardia and dyspnea although hemodynamically stable. Transthoracic echocardiography revealed a thrombus that was stuck into the patent foramen ovale with parts in right and left atria. Anticoagulation therapy was started; neither fibrinolytic therapy nor operation was performed because of low survey expectations of the patient's recently diagnosed primary disease stage IV lung cancer. Patient was discharged on his 20th day with oral anticoagulation and antiagregant therapy.

  6. Calcium Uptake and Release through Sarcoplasmic Reticulum in the Inferior Oblique Muscles of Patients with Inferior Oblique Overaction

    PubMed Central

    Kim, Hee Seon; Chang, Yoon-Hee; Kim, Do Han; Park, So Ra; Han, Sueng-Han

    2006-01-01

    We characterized and compared the characteristics of Ca2+ movements through the sarcoplasmic reticulum of inferior oblique muscles in the various conditions including primary inferior oblique overaction (IOOA), secondary IOOA, and controls, so as to further understand the pathogenesis of primary IOOA. Of 15 specimens obtained through inferior oblique myectomy, six were from primary IOOA, 6 from secondary IOOA, and the remaining 3 were controls from enucleated eyes. Ryanodine binding assays were performed, and Ca2+ uptake rates, calsequestrins and SERCA levels were determined. Ryanodine bindings and sarcoplasmic reticulum Ca2+ uptake rates were significantly decreased in primary IOOA (p<0.05). Western blot analysis conducted to quantify calsequestrins and SERCA, found no significant difference between primary IOOA, secondary IOOA, and the controls. Increased intracellular Ca2+ concentration due to reduced sarcoplasmic reticulum Ca2+ uptake may play a role in primary IOOA. PMID:16642550

  7. Tachyarrhythmias in acute myocardial infarction.

    PubMed

    McLean, K H; Bett, J N; Saltups, A

    1975-02-01

    In 1505 patients with acute myocardial infarction (MI) serious ventricular arrhythmias were commoner in those with transmural ECG changes, and were associated with an increase in mortality and in the incidence of left ventricular failure (LVF) as well as higher peak serum lactic dehydrogenase (LDH) levels. Atrial fibrillation (AF) occurred more often in older patients and in those with LVF and clinical evidence of pericarditis.

  8. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)

    PubMed Central

    Mavrakis, Konstantinos J; Van Der Meulen, Joni; Wolfe, Andrew L; Liu, Xiaoping; Mets, Evelien; Taghon, Tom; Khan, Aly A; Setty, Manu; Rondou, Pieter; Vandenberghe, Peter; Delabesse, Eric; Benoit, Yves; Socci, Nicholas B; Leslie, Christina S; Van Vlierberghe, Pieter; Speleman, Frank; Wendel, Hans-Guido

    2014-01-01

    The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer. PMID:21642990

  9. Idiopathic Thrombosis of the Inferior Vena Cava and Bilateral Femoral Veins in an Otherwise Healthy Male Soldier

    PubMed Central

    Gordon, Sarah; Kerns, Tamie; Londeree, William; Ching, Brian

    2013-01-01

    Thrombosis of the inferior vena cava is less common than deep venous thrombosis of the lower extremities, particularly in the absence of an obvious congenital caval abnormality or hypercoagulable state. We present a case of IVC thrombosis in an otherwise healthy and active 28-year-old male soldier secondary to dehydration and venous webbing. IVC thrombosis is an uncommon and underrecognized condition; in this case, the patient's caval thrombosis was initially mistaken for acute back strain. Prompt recognition is necessary to minimize long-term sequelae. PMID:24187556

  10. 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.

  11. 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…

  12. Inferior vena cava leiomyosarcoma: vascular reconstruction is not always mandatory

    PubMed Central

    Slimane, Maher; Yahia, Nada Belhaj; Bouaziz, Hanene; Bouzaine, Hatem; Benhassouna, Jamel; Dhieb, Tarek Ben; Hechiche, Monia; Gammoudi, Amor; Rahal, Khaled

    2016-01-01

    Leiomyosarcoma (LMS) of inferior vena cava is a rare and aggressive tumor, arising from the smooth muscle cells in the vessel wall. A large complete surgical resection is the essential treatment. The need of vascular reconstruction is not always mandatory. It’s above all to understand the place of the reconstruction with artificial vascular patch prosthetics of vena cave after a large resection of the tumor. We rapport two cases of LMS of inferior vena cava in two women who underwent successful large resection of tumor and lower segment of inferior vena cava. In first case, reconstruction of the inferior vena cava was not performed because of the development of venous collaterals derivation. In the second case reconstruction was done using Dacron interposition graft. The necessity of a large resection in management of primary leiomyosarcoma of vena cave makes sometimes unavoidable the sacrifice of a portion of the vena. Indeed, a better comprehension of the development of venous derivation may render unnecessary the reconstruction. PMID:28154642

  13. Traumatic longitudinal splitting of the inferior rectus muscle

    PubMed Central

    Laursen, Jessica; Demer, Joseph L.

    2011-01-01

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

  14. Inferior pancreaticoduodenal artery aneurysm associated with common hepatic artery occlusion.

    PubMed

    Bracale, G; Porcellini, M; Bernardo, B; Selvetella, L; Renda, A

    1996-12-01

    A unique case of true inferior pancreaticoduodenal artery aneurysm (IPDA) associated with occlusion of common hepatic artery is reported. Radiological and MRI findings are described. Because of high risk of visceral ischemia that contraindicated a percutaneous transluminal embolization, a successful tangential resection of aneurysm was performed.

  15. Endodontic-related inferior alveolar nerve and mental foramen paresthesia.

    PubMed

    Morse, D R

    1997-10-01

    Paresthesia is a condition that involves perverted sensations of pain, touch, or temperature. It has a variety of possible causes. This article presents a literature review and case reports of endodontically related inferior alveolar nerve and mental foramen paresthesia. Nondrug prevention methods and the dental uses of dexamethasone are also discussed.

  16. Cystitis - acute

    MedlinePlus

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

  17. Bioinformatics of cardiovascular miRNA biology.

    PubMed

    Kunz, Meik; Xiao, Ke; Liang, Chunguang; Viereck, Janika; Pachel, Christina; Frantz, Stefan; Thum, Thomas; Dandekar, Thomas

    2015-12-01

    MicroRNAs (miRNAs) are small ~22 nucleotide non-coding RNAs and are highly conserved among species. Moreover, miRNAs regulate gene expression of a large number of genes associated with important biological functions and signaling pathways. Recently, several miRNAs have been found to be associated with cardiovascular diseases. Thus, investigating the complex regulatory effect of miRNAs may lead to a better understanding of their functional role in the heart. To achieve this, bioinformatics approaches have to be coupled with validation and screening experiments to understand the complex interactions of miRNAs with the genome. This will boost the subsequent development of diagnostic markers and our understanding of the physiological and therapeutic role of miRNAs in cardiac remodeling. In this review, we focus on and explain different bioinformatics strategies and algorithms for the identification and analysis of miRNAs and their regulatory elements to better understand cardiac miRNA biology. Starting with the biogenesis of miRNAs, we present approaches such as LocARNA and miRBase for combining sequence and structure analysis including phylogenetic comparisons as well as detailed analysis of RNA folding patterns, functional target prediction, signaling pathway as well as functional analysis. We also show how far bioinformatics helps to tackle the unprecedented level of complexity and systemic effects by miRNA, underlining the strong therapeutic potential of miRNA and miRNA target structures in cardiovascular disease. In addition, we discuss drawbacks and limitations of bioinformatics algorithms and the necessity of experimental approaches for miRNA target identification. This article is part of a Special Issue entitled 'Non-coding RNAs'.

  18. 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

  19. Targeting miR-155 suppresses proliferation and induces apoptosis of HL-60 cells by targeting Slug/PUMA signal.

    PubMed

    Liang, Hui; Dong, Ziyan; Liu, Jiang-Feng; Chuang, Wei; Gao, Li-Zhen; Ren, Yu-Guo

    2016-10-27

    Recent studies have shown that high miR-155 expression was associated with poor prognosis in patients with acute myelogeneous leukemia (AML). Furthermore, targeting miR-155 results in monocytic differentiation and apoptosis. However, the exact role and mechanisms of miR-155 in human AML remains speculative. HL-60 cells were treated with anti-miR-155 for 72 h. Cell growth and apoptosis in vitro were detected by MTT, BrdU proliferation, colony formation and flow cytometry assay. The effect of anti-miR-155 on growth of HL-60 cells was also evaluated in a leukemia mouse model. Slug cDNA and PUMA siRNA trannsfection was used to assess the signal pathway. Different protein expression was detected by western blot assay and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. The results shown that targeting miR-155 resulted in a 24-fold decrease of miR-155 expression compared to negative control in the HL-60 cells. Targeting miR-155 significantly downregulated Slug and upregulated PUMA expression, and decreased HL-60 cell growth by 70% , impaired colony formation by approximately 60%, and increased HL-60 cell apoptosis by 45%. Targeting PUMA reversed miR-155 sliencing-induced proliferation and apoptosis of HL-60 cells. Restoration of Slug decreased PUMA expression. In murine engraftment models of HL-60 cells, we showed that targeting miR-155 was able to reduce tumor growth. This was accompanied with decreased Slug expression and increased PUMA expression in these tumors. Collectively, our findings strongly suggest targeting miR-155 exhibited in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of Slug expression and increase of PUMA expression.

  20. p53 activates miR-192-5p to mediate vancomycin induced AKI

    PubMed Central

    Chen, Jinwen; Wang, Juan; Li, Huiling; Wang, Shixuan; Xiang, Xudong; Zhang, Dongshan

    2016-01-01

    Pathogenic role of p53 in AKI remains controversial and the underlying mechanism is unclear. Here, we tested whether the inhibition of p53 may ameliorate vancomycin (VAN) induced acute kidney injury (AKI). Mice with p53 knock out (p53-KO) were resistant to VAN induced AKI, indicated by the analysis of renal function, histology, and apoptosis. Mechanistically, AKI was associated with the upregulation of several known p53 target genes, including Bax and p21, and this association was attenuated in p53-KO mice. Furthermore, the expression of miR-192-5p was significantly decreased in the p53-KO kidney tissues. In human renal tubular epithelial cell line (HK-2), VAN induced p53 accumulation and miR-192-5p expression. Both apoptosis of HK-2 cells and expression of miR-192-5p were also suppressed by pifithrin-α. Anti-miR-192-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells. Consistently, in vivo inhibition of miR-192-5p also suppressed VAN induced AKI. Thus, we provided clinical and genetic evidence that p53 was associated with the development of VAN induced AKI through upregulation of miR-192-5p. PMID:27941921

  1. 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

  2. MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

    PubMed

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Tejero, R; Díaz, T; Pratcorona, M; Tormo, M; Ribera, J M; Escoda, L; Duarte, R; Gallardo, D; Heras, I; Queipo de Llano, M P; Bargay, J; Monzo, M; Sierra, J; Navarro, A; Esteve, J

    2014-04-01

    Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

  3. miRDeep*: an integrated application tool for miRNA identification from RNA sequencing data.

    PubMed

    An, Jiyuan; Lai, John; Lehman, Melanie L; Nelson, Colleen C

    2013-01-01

    miRDeep and its varieties are widely used to quantify known and novel micro RNA (miRNA) from small RNA sequencing (RNAseq). This article describes miRDeep*, our integrated miRNA identification tool, which is modeled off miRDeep, but the precision of detecting novel miRNAs is improved by introducing new strategies to identify precursor miRNAs. miRDeep* has a user-friendly graphic interface and accepts raw data in FastQ and Sequence Alignment Map (SAM) or the binary equivalent (BAM) format. Known and novel miRNA expression levels, as measured by the number of reads, are displayed in an interface, which shows each RNAseq read relative to the pre-miRNA hairpin. The secondary pre-miRNA structure and read locations for each predicted miRNA are shown and kept in a separate figure file. Moreover, the target genes of known and novel miRNAs are predicted using the TargetScan algorithm, and the targets are ranked according to the confidence score. miRDeep* is an integrated standalone application where sequence alignment, pre-miRNA secondary structure calculation and graphical display are purely Java coded. This application tool can be executed using a normal personal computer with 1.5 GB of memory. Further, we show that miRDeep* outperformed existing miRNA prediction tools using our LNCaP and other small RNAseq datasets. miRDeep* is freely available online at http://www.australianprostatecentre.org/research/software/mirdeep-star.

  4. 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

  5. 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…

  6. 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.

  7. Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis

    PubMed Central

    Wu, Jingwen; Bao, Jianqiang; Kim, Minkyung; Yuan, Shuiqiao; Tang, Chong; Zheng, Huili; Mastick, Grant S.; Xu, Chen; Yan, Wei

    2014-01-01

    Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encoding five miRNAs (miR-34b, miR-34c, miR-449a, miR-449b, and miR-449c) led to sexually dimorphic, partial perinatal lethality, growth retardation, and infertility. These developmental defects correlated with the dysregulation of ∼240 target genes, which are mainly involved in three major cellular functions, including cell-fate control, brain development and microtubule dynamics. Our data demonstrate an essential role of a miRNA family in brain development, motile ciliogenesis, and spermatogenesis. PMID:24982181

  8. miRLocator: Machine Learning-Based Prediction of Mature MicroRNAs within Plant Pre-miRNA Sequences.

    PubMed

    Cui, Haibo; Zhai, Jingjing; Ma, Chuang

    2015-01-01

    MicroRNAs (miRNAs) are a class of short, non-coding RNA that play regulatory roles in a wide variety of biological processes, such as plant growth and abiotic stress responses. Although several computational tools have been developed to identify primary miRNAs and precursor miRNAs (pre-miRNAs), very few provide the functionality of locating mature miRNAs within plant pre-miRNAs. This manuscript introduces a novel algorithm for predicting miRNAs named miRLocator, which is based on machine learning techniques and sequence and structural features extracted from miRNA:miRNA* duplexes. To address the class imbalance problem (few real miRNAs and a large number of pseudo miRNAs), the prediction models in miRLocator were optimized by considering critical (and often ignored) factors that can markedly affect the prediction accuracy of mature miRNAs, including the machine learning algorithm and the ratio between training positive and negative samples. Ten-fold cross-validation on 5854 experimentally validated miRNAs from 19 plant species showed that miRLocator performed better than the state-of-art miRNA predictor miRdup in locating mature miRNAs within plant pre-miRNAs. miRLocator will aid researchers interested in discovering miRNAs from model and non-model plant species.

  9. miRLocator: Machine Learning-Based Prediction of Mature MicroRNAs within Plant Pre-miRNA Sequences

    PubMed Central

    Cui, Haibo; Zhai, Jingjing; Ma, Chuang

    2015-01-01

    MicroRNAs (miRNAs) are a class of short, non-coding RNA that play regulatory roles in a wide variety of biological processes, such as plant growth and abiotic stress responses. Although several computational tools have been developed to identify primary miRNAs and precursor miRNAs (pre-miRNAs), very few provide the functionality of locating mature miRNAs within plant pre-miRNAs. This manuscript introduces a novel algorithm for predicting miRNAs named miRLocator, which isbased on machine learning techniques and sequence and structural features extracted from miRNA:miRNA* duplexes. To address the class imbalance problem (few real miRNAs and a large number of pseudo miRNAs), the prediction models in miRLocator were optimized by considering critical (and often ignored) factors that can markedly affect the prediction accuracy of mature miRNAs, including the machine learning algorithm and the ratio between training positive and negative samples. Ten-fold cross-validation on 5854 experimentally validated miRNAs from 19 plant species showed that miRLocator performed better than the state-of-art miRNA predictor miRdup in locating mature miRNAs within plant pre-miRNAs. miRLocator will aid researchers interested in discovering miRNAs from model and non-model plant species. PMID:26558614

  10. Care of patients with deep inferior epigastric perforator reconstruction.

    PubMed

    Long, Laura; Israelian, Amy

    2013-01-01

    Recent trends reflect greater numbers of women opting for mastectomy for invasive breast cancer. Breast reconstruction, either at the time of mastectomy or later, is increasingly an option patients prefer. Although many women opt for implants, reconstruction using autologous tissue offers several advantages including tissue that feels more natural and will age naturally with the patient. The deep inferior epigastric perforator flap has emerged as an alternative to the transverse rectus abdominis myocutaneous flap and allows for preservation of the underlying abdominal muscle. As greater numbers of surgeons are able to offer this microvascular alternative, nurses will care for these postoperative patients in the intensive care unit and medical/surgical settings. This article reviews the evaluation of patients for deep inferior epigastric perforator reconstruction and the unique complexities of postoperative nursing care for these patients.

  11. Enhanced Modiolar Stimulation Effects in the Inferior Colliculus

    DTIC Science & Technology

    2007-11-02

    stimulation. Keywords: Cochlear Implant , Inferior Colliculus, Modiolar Stimulation I. INTRODUCTION Cochlear implants are used to provide hearing sensation...to the sensoneurally deaf. Bipolar electrical stimulation of a scala tympani cochlear implant produces a localized stimulus which has been measured...to diminish at about 9dB/octave [1]. Blamey et al. (1994) describes both a perceived low frequency shift by cochlear implant patients in response to

  12. Management of the Thrombosed Filter-Bearing Inferior Vena Cava

    PubMed Central

    Sildiroglu, Onur; Ozer, Harun; Turba, Ulku Cenk

    2012-01-01

    Inferior vena cava (IVC) filter thrombosis is a complex problem. Thrombus within an IVC filter may range from an asymptomatic small thrombus to critical IVC occlusion that affects both lower extremities. The published experience of IVC thrombosis management in relation to filters is either anecdotal or limited to a small group of patients; however, endovascular treatment methods appear to be safe and effective in patients with IVC thrombosis. This review focuses on filter-related IVC thrombosis and its endovascular management. PMID:23449290

  13. Leiomyosarcoma of the inferior vena cava: a case report.

    PubMed

    Nascif, Rafael Lemos; Antón, Ana Graziela Santana; Fernandes, Gabriel Lacerda; Dantas, George Caldas; Gomes, Vinícius de Araújo; Natal, Marcelo Ricardo Canuto

    2014-01-01

    The authors report a case of a 48 year-old female patient with moderate abdominal pain and bulging in the abdomen. Physical examination demonstrated the presence of a palpable abdominal mass. Computed tomography showed a heterogeneously enhancing retroperitoneal mass in close contact with the inferior vena cava. En bloc resection of the mass and of the attached vena cava segment was performed. Histological analysis revealed leiomyosarcoma.

  14. [Aneurysm of the anterior inferior cerebellar artery: case report].

    PubMed

    Adorno, Juan Oscar Alarcón; de Andrade, Guilherme Cabral

    2002-12-01

    The intracranial aneurysms of the posterior circulation have been reported between 5 and 10% of all cerebral aneurysms and the aneurysms of the anterior inferior cerebellar artery (AICA) are considered rare, can cause cerebello pontine angle (CPA) syndrome with or without subarachnoid hemorrhage. Since 1948 few cases were described in the literature. We report on a 33 year-old female patient with subarachnoid hemorrhage due to sacular aneurysm of the left AICA. She was submitted to clipage of the aneurysm without complications.

  15. Truncal ataxia from infarction involving the inferior olivary nucleus.

    PubMed

    Park, Jae Hyun; Ryoo, Sookyung; Moon, So Young; Seo, Sand Won; Na, Duk L

    2012-08-01

    Truncal ataxia in medullary infarction may be caused by involvement of the lateral part of the medulla; however, truncal ataxia in infarction involving the inferior olivary nucleus (ION) has received comparatively little attention. We report a patient with truncal ataxia due to medial medullary infarction located in the ION. A lesion in the ION could produce a contralateral truncal ataxia due to increased inhibitory input to the contralesional vestibular nucleus from the contralesional flocculus.

  16. 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.

  17. Bayesian approach to non-inferiority trials for normal means.

    PubMed

    Gamalo, M Amper; Wu, Rui; Tiwari, Ram C

    2016-02-01

    Regulatory framework recommends that novel statistical methodology for analyzing trial results parallels the frequentist strategy, e.g. the new method must protect type-I error and arrive at a similar conclusion. Keeping these in mind, we construct a Bayesian approach for non-inferiority trials with normal response. A non-informative prior is assumed for the mean response of the experimental treatment and Jeffrey's prior for its corresponding variance when it is unknown. The posteriors of the mean response and variance of the treatment in historical trials are then assumed as priors for its corresponding parameters in the current trial, where that treatment serves as the active control. From these priors, a Bayesian decision criterion is derived to determine whether the experimental treatment is non-inferior to the active control. This criterion is evaluated and compared with the frequentist method using simulation studies. Results show that both Bayesian and frequentist approaches perform alike, but the Bayesian approach has a higher power when the variances are unknown. Both methods also arrive at the same conclusion of non-inferiority when applied on two real datasets. A major advantage of the proposed Bayesian approach lies in its ability to provide posterior probabilities for varying effect sizes of the experimental treatment over the active control.

  18. Abducens nerve palsy due to inferior petrosal sinus thrombosis.

    PubMed

    Mittal, Shivam Om; Siddiqui, Junaid; Katirji, Bashar

    2017-02-24

    Isolated unilateral abducens nerve palsy is usually due to ischemia, trauma or neoplasm. Dorello's canal is the space between the petrous apex and superolateral portion of the clivus, bound superiorly by Gruber's ligament. The abducens nerve travels with inferior petrosal sinus (IPS) though the Dorello's canal before entering the cavernous sinus. A 31-year-old man presented with neck pain, and binocular horizontal diplopia, worse looking towards left and at distance. He had a history of intravenous drug abuse but no history of hypertension or diabetes. On examination, he had complete left 6th nerve palsy with normal fundi, pupils, and other cranial nerves. Methicillin-resistant Staphylococcus aureus bacteremia was detected with naïve tricuspid valve endocarditis and multiple septic emboli to lungs with infarcts. His cerebrospinal fluid was normal. MRI of the brain was normal. MRV of head and neck showed thrombosis of the left internal jugular vein, left sigmoid sinus and left inferior petrosal sinus with normal cavernous sinus and no evidence of mastoiditis. He was treated with broad spectrum antibiotics. He was not anticoagulated for fear of pulmonary hemorrhage from pulmonary infarcts. Although cerebral venous sinus thrombosis commonly presents with elevated intracranial pressure, isolated ipsilateral 6th nerve palsy from its compression in Dorello's canal due to thrombosis of the ipsilateral inferior petrosal sinus is extremely rare. To our knowledge, only two patients have been reported with isolated abducens palsy due to IPS thrombosis; one caused by septic emboli and the other developed it during IPS cortisol level sampling.

  19. Inferior vestibular neuritis in a fighter pilot: a case report.

    PubMed

    Xie, Su Jiang; Jia, Hong Bo; Xu, Po; Zheng, Ying Juan

    2013-06-01

    Spatial disorientation in airplane pilots is a leading factor in many fatal flying accidents. Spatial orientation is the product of integrative inputs from the proprioceptive, vestibular, and visual systems. One condition that can lead to sudden pilot incapacitation in flight is vestibular neuritis. Vestibular neuritis is commonly diagnosed by a finding of unilateral vestibular failure, such as a loss of caloric response. However, because caloric response testing reflects the function of only the superior part of the vestibular nerve, it cannot detect cases of neuritis in only the inferior part of the nerve. We describe the case of a Chinese naval command fighter pilot who exhibited symptoms suggestive of vestibular neuritis but whose caloric response test results were normal. Further testing showed a unilateral loss of vestibular evoked myogenic potentials (VEMPs). We believe that this pilot had pure inferior nerve vestibular neuritis. VEMP testing plays a major role in the diagnosis of inferior nerve vestibular neuritis in pilots. We also discuss this issue in terms of aeromedical concerns.

  20. [Inferior vertical nystagmus: is magnetic resonance imaging mandatory?].

    PubMed

    Esteban-Sánchez, Jonathan; Rueda-Marcos, Almudena; Sanz-Fernández, Ricardo; Martín-Sanz, Eduardo

    2016-02-01

    Introduccion. La aparicion de un nistagmo vertical inferior clasicamente obliga a descartar una patologia vascular o de la union craneocervical mediante resonancia magnetica (RM). Estudios recientes demuestran una baja rentabilidad de esta prueba, ya que sugieren que este signo oculomotor puede tener una causa vestibular periferica, sobre todo cuando el paciente presenta un vertigo posicional paroxistico benigno (VPPB) del canal semicircular superior. Objetivo. Comprobar la rentabilidad de la RM en una poblacion de pacientes con nistagmo de posicion vertical inferior. Pacientes y metodos. Estudio retrospectivo de 42 pacientes consecutivos a los que se les realizo una historia clinica, exploracion fisica, y pruebas vestibulares caloricas y rotatorias. A todos ellos se les practico una RM craneal y cervical. Resultados. El 52% de los pacientes con nistagmo de posicion vertical inferior presentaba una clinica y exploracion fisica compatibles con VPPB del canal semicircular superior. La RM fue normal en un 67%, un 26% mostraba datos de espondilopatia y un 5% de microangiopatia cerebral no relacionados con la clinica del paciente. La prevalencia de malformacion de Arnold-Chiari de tipo I fue de un 9% en la poblacion estudiada, sin que nadie tuviera un antecedente reciente de VPPB. Los resultados obtenidos en las pruebas complementarias vestibulares no aportaron informacion adicional para llegar a un diagnostico etiologico. Conclusion. En los pacientes con un VPPB, la RM craneal y las pruebas vestibulares tienen una baja rentabilidad diagnostica, y se debe evaluar la necesidad real de esta prueba con el contexto clinico.

  1. Intraosseous schwannoma originating in inferior alveolar nerve: a case report.

    PubMed

    Suga, Kenichiro; Ogane, Satoru; Muramatsu, Kyotaro; Ohata, Hitoshi; Uchiyama, Takeshi; Takano, Nobuo; Shibahara, Takahiko; Eguchi, Jun; Murakami, Satoshi; Matsuzaka, Kenichi

    2013-01-01

    Schwannomas (neurilemmomas) are benign neoplasms derived from Schwann cells of the neurilemma and appear most frequently on the auditory nerve or peripheral nerves of the skin. They arise in the oral and maxillofacial region infrequently, and very rarely in the center of the jaw. We herein present a case of a rare mandibular intraosseous schwannoma derived from the main trunk of the inferior alveolar nerve in a 33-year-old man. Fusiform expansion in the mandibular canal was observed and a mass showing the target sign in the mandibular canal was confirmed on T2-weighted and Gd contrastenhanced T1-weighted MRI. Based on these findings, an inferior alveolar nerve-derived schwannoma or other benign nervous system neoplasm was diagnosed. A buccal side cortical bone flap in the mandibular molar region was removed to expose the mass, which was then peeled away from the nerve fibers and completely removed. Some inferior alveolar nerve fibers that were connected to the mass were removed at the same time, but the remaining nerve fiber bundle was preserved. Histopathology confirmed the diagnosis of a schwannoma with Antoni type A and Antoni type B regions. Although the patient experienced extremely mild paresthesia in the skin over the mental region and mental foramen at immediately after surgery, this had almost entirely disappeared at 7 years and 4 months later, and there has been no tumor recurrence.

  2. 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

  3. Downregulation of miR-205 Modulates Cell Susceptibility to Oxidative and Endoplasmic Reticulum Stresses in Renal Tubular Cells

    PubMed Central

    Muratsu-Ikeda, Shiyo; Nangaku, Masaomi; Ikeda, Yoichiro; Tanaka, Tetsuhiro; Wada, Takehiko; Inagi, Reiko

    2012-01-01

    Background Oxidative stress and endoplasmic reticulum (ER) stress play a crucial role in tubular damage in both acute kidney injury (AKI) and chronic kidney disease (CKD). While the pathophysiological contribution of microRNAs (miRNA) to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. Methods We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS) level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3′-UTR-luciferase assay. Results We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3′-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2) gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. Conclusions miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules. PMID:22859986

  4. Knockout of miR-221 and miR-222 reveals common and specific targets for paralogous miRNAs.

    PubMed

    Jeong, Geon; Lim, Yeong-Hwan; Kim, Nam Joong; Wee, Gabbine; Kim, Young-Kook

    2017-02-01

    MicroRNAs (miRNAs) regulate the expression of mRNA through sequence-specific binding of the 3' untranslated region (UTR). The seed sequence of miRNAs is the key determinant for target site recognition. Paralogous miRNAs, which share the same seed sequences but differ in their 3' regions, are known to regulate largely overlapping groups of mRNAs. However, no study has analyzed functional differences between paralogous miRNAs with proper experimental methods. In this study, we compared the targets of paralogous miRNAs, miR-221 and miR-222. Using a nuclease-mediated genome engineering technique, we established knockout cell lines for these miRNAs, and precisely analyzed differences in target regulation. We found that miR-221 and miR-222 suppress the previously identified targets, CDKN1B and CDKN1C, differentially. Whereas both miRNAs suppressed CDKN1B, only miR-221 suppressed CDKN1C. From transcriptome analyses, we found that several different target mRNAs were regulated by each of miR-221 and miR-222 independently, although a large number of mRNAs responded commonly to miR-221 and miR-222. This is the first study to compare the mRNA regulations by paralogous miRNAs and illustrate that paralogous miRNAs with the same seed sequence also have difference in target regulation.

  5. <mi mathvariant='script'>PTmi>-symmetric slowing down of decoherence

    SciTech Connect

    Gardas, Bartlomiej; Deffner, Sebastian; Saxena, Avadh Behari

    2016-10-27

    Here, we investigate <mi mathvariant='script'>PTmi>-symmetric quantum systems ultraweakly coupled to an environment. We find that such open systems evolve under <mi mathvariant='script'>PTmi>-symmetric, purely dephasing and unital dynamics. The dynamical map describing the evolution is then determined explicitly using a quantum canonical transformation. Furthermore, we provide an explanation of why <mi mathvariant='script'>PTmi>-symmetric dephasing-type interactions lead to a critical slowing down of decoherence. This effect is further exemplified with an experimentally relevant system, a <mi mathvariant='script'>PTmi>-symmetric qubit easily realizable, e.g., in optical or microcavity experiments.

  6. 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.

  7. Acute Diagnosis and Management of Stroke Presenting Dizziness or Vertigo.

    PubMed

    Lee, Seung-Han; Kim, Ji-Soo

    2015-08-01

    Stroke involving the brainstem and cerebellum frequently presents acute vestibular syndrome. Although vascular vertigo is known to usually accompany other neurologic symptoms and signs, isolated vertigo from small infarcts involving the cerebellum or brainstem has been increasingly recognized. Bedside neuro-otologic examination can reliably differentiate acute vestibular syndrome due to stroke from more benign inner ear disease. Sometimes acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Accurate identification of isolated vascular vertigo is very important because misdiagnosis of acute stroke may result in significant morbidity and mortality.

  8. 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

  9. Thermal evolution of antiferromagnetic correlations and tetrahedral bond angles in superconducting <mi mathvariant='normal'>FeTemi>1<mi>x mathvariant='normal'>Semi>x>

    SciTech Connect

    Xu, Zhijun; Schneeloch, J. A.; Wen, Jinsheng; Božin, E. S.; Granroth, G. E.; Winn, B. L.; Feygenson, M.; Birgeneau, R. J.; Gu, Genda; Zaliznyak, I. A.; Tranquada, J. M.; Xu, Guangyong

    2016-03-14

    It has recently been demonstrated that dynamical magnetic correlations measured by neutron scattering in iron chalcogenides can be described with models of short-range correlations characterized by particular choices of four-spin plaquettes, where the appropriate choice changes as the parent material is doped towards superconductivity. Here we apply such models to describe measured maps of magnetic scattering as a function of two-dimensional wave vectors obtained for optimally superconducting crystals of <mi mathvariant='normal'>FeTemi>1<mi>x mathvariant='normal'>Semi>x>. We show that the characteristic antiferromagnetic wave vector evolves from that of the bicollinear structure found in underdoped chalcogenides (at high temperature) to that associated with the stripe structure of antiferromagnetic iron arsenides (at low temperature); these can both be described with the same local plaquette, but with different interplaquette correlations. While the magnitude of the low-energy magnetic spectral weight is substantial at all temperatures, it actually weakens somewhat at low temperature, where the charge carriers become more itinerant. The observed change in spin correlations is correlated with the dramatic drop in the electronic scattering rate and the growth of the bulk nematic response upon cooling. In conclusion, we also present powder neutron diffraction results for lattice parameters in <mi mathvariant='normal'>FeTemi>1<mi>x mathvariant='normal'>Semi>x> indicating that the tetrahedral bond angle tends to increase towards the ideal value upon cooling, in agreement with the increased screening of the crystal field by more itinerant electrons and the correspondingly smaller splitting of the Fe 3d orbitals.

  10. 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

  11. Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer

    PubMed Central

    Bajan, Sarah; Hutvagner, Gyorgy

    2014-01-01

    The majority of human protein-coding genes are predicted to be targets of miRNA-mediated post-transcriptional regulation. The widespread influence of miRNAs is illustrated by their essential roles in all biological processes. Regulated miRNA expression is essential for maintaining cellular differentiation; therefore alterations in miRNA expression patterns are associated with several diseases, including various cancers. High-throughput sequencing technologies revealed low level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence, length, target preference and expression patterns from their parental miRNA and can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent to the miRNA gene. The association between isomiR expression and disease progression is largely unknown. Misregulated miRNA expression is thought to contribute to the formation and/or progression of cancer. However, due to the diversity of targeted transcripts, miRNAs can function as both tumor-suppressor genes and oncogenes as defined by cellular context. Despite this, miRNA profiling studies concluded that the differential expression of particular miRNAs in diseased tissue could aid the diagnosis and treatment of some cancers. PMID:25069508

  12. 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

  13. 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

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

    PubMed

    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.

  15. Cell-type-specific miR-431 dysregulation in a motor neuron model of spinal muscular atrophy.

    PubMed

    Wertz, Mary H; Winden, Kellen; Neveu, Pierre; Ng, Shi-Yan; Ercan, Ebru; Sahin, Mustafa

    2016-06-01

    Spinal muscular atrophy (SMA) is an autosomal-recessive pediatric neurodegenerative disease characterized by selective loss of spinal motor neurons. It is caused by mutation in the survival of motor neuron 1, SMN1, gene and leads to loss of function of the full-length SMN protein. microRNAs (miRNAs) are small RNAs that are involved in post-transcriptional regulation of gene expression. Prior studies have implicated miRNAs in the pathogenesis of motor neuron disease. We hypothesized that motor neuron-specific miRNA expression changes are involved in their selective vulnerability in SMA. Therefore, we sought to determine the effect of SMN loss on miRNAs and their target mRNAs in spinal motor neurons. We used microarray and RNAseq to profile both miRNA and mRNA expression in primary spinal motor neuron cultures after acute SMN knockdown. By integrating the miRNA:mRNA profiles, a number of dysregulated miRNAs were identified with enrichment in differentially expressed putative mRNA targets. miR-431 expression was highly increased, and a number of its putative mRNA targets were significantly downregulated in motor neurons after SMN loss. Further, we found that miR-431 regulates motor neuron neurite length by targeting several molecules previously identified to play a role in motor neuron axon outgrowth, including chondrolectin. Together, our findings indicate that cell-type-specific dysregulation of miR-431 plays a role in the SMA motor neuron phenotype.

  16. [Acute thrombosis of the infrarenal aorta].

    PubMed

    Napolitano, A M; Napolitano, L; Marinucci, R; Colalongo, C; Ucchino, S

    1998-05-01

    The Authors report three cases of patients operated for acute thrombotic aortic occlusion. All the three patients were treated with an aortic transabdominal approach, thromboendarteriectomy and aorto-femoral by-pass. In two patients the result was satisfying, one with a late and partial recovery of the motility of the inferior limbs. One patient died for heart failure in eighth postoperative day. The Authors believe that this unsatisfying result was caused by delay in the surgical treatment (almost 30 hours).

  17. The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions.

    PubMed

    Simon, David J; Madison, Jon M; Conery, Annie L; Thompson-Peer, Katherine L; Soskis, Michael; Ruvkun, Gary B; Kaplan, Joshua M; Kim, John K

    2008-05-30

    We show that miR-1, a conserved muscle-specific microRNA, regulates aspects of both pre- and postsynaptic function at C. elegans neuromuscular junctions. miR-1 regulates the expression level of two nicotinic acetylcholine receptor (nAChR) subunits (UNC-29 and UNC-63), thereby altering muscle sensitivity to acetylcholine (ACh). miR-1 also regulates the muscle transcription factor MEF-2, which results in altered presynaptic ACh secretion, suggesting that MEF-2 activity in muscles controls a retrograde signal. The effect of the MEF-2-dependent retrograde signal on secretion is mediated by the synaptic vesicle protein RAB-3. Finally, acute activation of levamisole-sensitive nAChRs stimulates MEF-2-dependent transcriptional responses and induces the MEF-2-dependent retrograde signal. We propose that miR-1 refines synaptic function by coupling changes in muscle activity to changes in presynaptic function.

  18. Molecular inotropy mediated by cardiac miR-based PDE4D/PRKAR1α/phosphoprotein signaling

    PubMed Central

    Bedada, Fikru B.; Martindale, Joshua J.; Arden, Erik; Metzger, Joseph M.

    2016-01-01

    Molecular inotropy refers to cardiac contractility that can be modified to affect overall heart pump performance. Here we show evidence of a new molecular pathway for positive inotropy by a cardiac-restricted microRNA (miR). We report enhanced cardiac myocyte performance by acute titration of cardiac myosin-embedded miR-208a. The observed positive effect was independent of host gene myosin effects with evidence of negative regulation of cAMP-specific 3′,5′-cyclic phosphodiesterase 4D (PDE4D) and the regulatory subunit of PKA (PRKAR1α) content culminating in PKA-site dependent phosphorylation of cardiac troponin I (cTnI) and phospholamban (PLN). Further, acute inhibition of miR-208a in adult myocytes in vitro increased PDE4D expression causing reduced isoproterenol-mediated phosphorylation of cTnI and PLN. Next, rAAV-mediated miR-208a gene delivery enhanced heart contractility and relaxation parameters in vivo. Finally, acute inducible increases in cardiac miR-208a in vivo reduced PDE4D and PRKAR1α, with evidence of increased content of several complementary miRs harboring the PDE4D recognition sequence. Physiologically, this resulted in significant cardiac cTnI and PLN phosphorylation and improved heart performance in vivo. As phosphorylation of cTnI and PLN is critical to myocyte function, titration of miR-208a represents a potential new mechanism to enhance myocardial performance via the PDE4D/PRKAR1α/PKA phosphoprotein signaling pathway. PMID:27833092

  19. Single nucleotide seed modification restores in vivo tolerability of a toxic artificial miRNA sequence in the mouse brain.

    PubMed

    Monteys, Alex Mas; Spengler, Ryan M; Dufour, Brett D; Wilson, Matt S; Oakley, Clayton K; Sowada, Matt J; McBride, Jodi L; Davidson, Beverly L

    2014-12-01

    Huntington's disease is a fatal neurodegenerative disease caused by polyglutamine-expansion in huntingtin (HTT). Recent work showed that gene silencing approaches, including RNA interference (RNAi), improve disease readouts in mice. To advance RNAi to the clinic, we designed miHDS1, with robust knockdown of human HTT and minimized silencing of unintended transcripts. In Rhesus macaque, AAV delivery of miHDS1 to the putamen reduced HTT expression with no adverse effects on neurological status including fine and gross motor skills, no immune activation and no induction of neuropathology out to 6 weeks post injection. Others showed safety of a different HTT-targeting RNAi in monkeys for 6 months. Application of miHDS1 to Huntington's patients requires further safety testing in normal rodents, despite the fact that it was optimized for humans. To satisfy this regulatory requirement, we evaluated normal mice after AAV.miHDS1 injection. In contrast to monkeys, neurological deficits occurred acutely in mice brain and was attributed to off-target silencing through interactions of miHDS1 with the 3'UTR of other transcripts. While we resolved miHDS1 toxicity in mouse brain and maintained miHDS1-silencing efficacy, these studies highlight that optimizing nucleic acid-based medicines for safety in humans presents challenges for safety testing in rodents or other distantly related species.

  20. Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host Disease in the Rat

    PubMed Central

    Jalapothu, Dasaradha; Boieri, Margherita; Crossland, Rachel E.; Shah, Pranali; Butt, Isha A.; Norden, Jean; Dressel, Ralf; Dickinson, Anne M.; Inngjerdingen, Marit

    2016-01-01

    MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate

  1. Anesthetic technique for inferior alveolar nerve block: a new approach

    PubMed Central

    PALTI, Dafna Geller; de ALMEIDA, Cristiane Machado; RODRIGUES, Antonio de Castro; ANDREO, Jesus Carlos; LIMA, José Eduardo Oliveira

    2011-01-01

    Background Effective pain control in Dentistry may be achieved by local anesthetic techniques. The success of the anesthetic technique in mandibular structures depends on the proximity of the needle tip to the mandibular foramen at the moment of anesthetic injection into the pterygomandibular region. Two techniques are available to reach the inferior alveolar nerve where it enters the mandibular canal, namely indirect and direct; these techniques differ in the number of movements required. Data demonstrate that the indirect technique is considered ineffective in 15% of cases and the direct technique in 1329% of cases. Objective Objective: The aim of this study was to describe an alternative technique for inferior alveolar nerve block using several anatomical points for reference, simplifying the procedure and enabling greater success and a more rapid learning curve. Materials and Methods A total of 193 mandibles (146 with permanent dentition and 47 with primary dentition) from dry skulls were used to establish a relationship between the teeth and the mandibular foramen. By using two wires, the first passing through the mesiobuccal groove and middle point of the mesial slope of the distolingual cusp of the primary second molar or permanent first molar (right side), and the second following the oclusal plane (left side), a line can be achieved whose projection coincides with the left mandibular foramen. Results The obtained data showed correlation in 82.88% of cases using the permanent first molar, and in 93.62% of cases using the primary second molar. Conclusion This method is potentially effective for inferior alveolar nerve block, especially in Pediatric Dentistry. PMID:21437463

  2. Inferior epigastric artery: Surface anatomy, prevention and management of injury.

    PubMed

    Wong, Clare; Merkur, Harry

    2016-04-01

    The anatomical position of the inferior epigastric artery (IEA) subjects it to risk of injury during abdominal procedures that are close to the artery, such as laparoscopic trocar insertion, insertion of intra-abdominal drains, Tenckhoff(®) catheter (peritoneal dialysis catheter) and paracentesis. This article aims to raise the awareness of the anatomical variations of the course of the IEA in relation to abdominal landmarks in order to define a safer zone for laparoscopic ancillary trocar placement. Methods of managing the IEA injury as well as techniques to minimise the risk of injury to the IEA are reviewed and discussed.

  3. CT fluoroscopic guided insertion of inferior vena cava filters.

    PubMed

    Ignotus, P; Wetton, C; Berry, J

    2006-03-01

    The value and use of inferior vena cava (IVC) filters is well documented and has been growing since the first reported filter placement in 1973 and the first percutaneous insertion in 1982. Access routes now include both jugular veins, both ante-cubital veins and both femoral veins. However, all insertions require some form of imaging, usually fluoroscopy, to identify the location of the filter with respect to the IVC and the renal veins. We describe two cases where the patients' weight was significantly greater than the weight limit of the angiography table, necessitating insertion under CT fluoroscopic guidance.

  4. A Novel Technique for Inferior Vena Cava Filter Extraction

    SciTech Connect

    Johnston, Edward William Rowe, Luke Michael Morgan; Brookes, Jocelyn; Raja, Jowad; Hague, Julian

    2013-05-02

    Inferior vena cava (IVC) filters are used to protect against pulmonary embolism in high-risk patients. Whilst the insertion of retrievable IVC filters is gaining popularity, a proportion of such devices cannot be removed using standard techniques. We describe a novel approach for IVC filter removal that involves snaring the filter superiorly along with the use of flexible forceps or laser devices to dissect the filter struts from the caval wall. This technique has used to successfully treat three patients without complications in whom standard techniques failed.

  5. Inferior alveolar nerve paresthesia relieved by microscopic endodontic treatment.

    PubMed

    Yatsuhashi, Takaaki; Nakagawa, Kan-Ichi; Matsumoto, Miho; Kasahara, Masataka; Igarashi, Tomoko; Ichinohe, Tatsuya; Kaneko, Yuzuru

    2003-11-01

    We experienced two cases of inferior alveolar nerve paresthesia caused by root canal medicaments, which were successfully relieved by microscopic endodontic treatment. In the first case, the paresthesia might have been attributable to infiltration of calcium hydroxide into the mandibular canal through the root canals of the mandibular left second molar tooth. In the second case, the paresthesia might have been attributable to infiltration of paraformaldehyde through the root canals of the mandibular right second molar tooth. The paresthesia was relieved in both cases by repetitive microscopic endodontic irrigation using physiological saline solution in combination with oral vitamin B12 and adenosine triphosphate.

  6. Duplicate inferior vena cava filters: more is not always better.

    PubMed

    Katyal, Anup; Javed, Muhammad Ali

    2016-01-01

    Duplication of the inferior vena cava (IVC) has been reported in literature. This achieves clinical significance in the setting of lower extremity venous thromboembolism with a contraindication for anticoagulation. We describe a case of lower extremity deep vein thrombosis with duplicate IVC. Anticoagulation was contraindicated in this case leading to successful treatment with double IVC filters. We conducted a PubMed search for all current English language published literature, where filters were placed in the presence of duplicate IVC. We suggest that patients with deep vein thrombosis should have an accurate assessment of venous anatomy before IVC filter placement. Duplication of IVC, although rare, should be considered as this has management implications.

  7. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  8. Strong anisotropy and magnetostriction in the two-dimensional Stoner ferromagnet <mi>Fe>3<mi>GeTe>2

    SciTech Connect

    Zhuang, Houlong L.; Kent, P. R. C.; Hennig, Richard G.

    2016-04-06

    Computationally characterizing magnetic properies of novel two-dimensional (2D) materials serves as an important first step of exploring possible applications. Using density-functional theory, we show that single-layer <mi>Fe>3<mi>GeTe>2 is a potential 2D material with sufficiently low formation energy to be synthesized by mechanical exfoliation from the bulk phase with a van der Waals layered structure. In addition, we calculated the phonon dispersion demonstrating that single-layer <mi>Fe>3<mi>GeTe>2is dynamically stable. Furthermore, we find that similar to the bulk phase, 2D <mi>Fe>3<mi>GeTe>2 exhibits amagnetic moment that originates from a Stoner instability. In contrast to other 2D materials, we find that single-layer <mi>Fe>3<mi>GeTe>2 exhibits a significant uniaxial magnetocrystalline anisotropy energy of 920μ eV per Fe atom originating from spin-orbit coupling. In conclusion, we show that applying biaxial tensile strains enhances the anisotropy energy, which reveals strong magnetostriction in single-layer <mi>Fe>3<mi>GeTe>2 with a sizable magneostrictive coefficient. Our results indicate that single-layer <mi>Fe>3<mi>GeTe>2 is potentially useful for magnetic storage applications.

  9. From conventional therapy toward microRNA-based therapy in acute promyelocytic leukemia

    PubMed Central

    Ehtesham, Naeim; Sharifi, Mohammadreza

    2016-01-01

    Acute promyelocytic leukemia (APL) is a hematopoietic malignancy that is known with its special cytogenetic feature. Several studies have surveyed expression signature of microRNAs (miRNAs) in APL patients, especially patients who are treated with conventional therapy of this disease. Using miRNAs as diagnostic or prognostic biomarkers in various cancers has been widely studied. Currently, most studies are focusing on exploiting miRNAs as therapeutic tools, and promising progress has been achieved in this field. Recently, studies in the field of miRNA-based therapy in APL have been started. PMID:28028527

  10. MiRNAs and miRNA Polymorphisms Modify Drug Response

    PubMed Central

    Li, Mu-Peng; Hu, Yao-Dong; Hu, Xiao-Lei; Zhang, Yan-Jiao; Yang, Yong-Long; Jiang, Chun; Tang, Jie; Chen, Xiao-Ping

    2016-01-01

    Differences in expression of drug response-related genes contribute to inter-individual variation in drugs’ biological effects. MicroRNAs (miRNAs) are small noncoding RNAs emerging as new players in epigenetic regulation of gene expression at post-transcriptional level. MiRNAs regulate the expression of genes involved in drug metabolism, drug transportation, drug targets and downstream signal molecules directly or indirectly. MiRNA polymorphisms, the genetic variations affecting miRNA expression and/or miRNA-mRNA interaction, provide a new insight into the understanding of inter-individual difference in drug response. Here, we provide an overview of the recent progress in miRNAs mediated regulation of biotransformation enzymes, drug transporters, and nuclear receptors. We also describe the implications of miRNA polymorphisms in cancer chemotherapy response. PMID:27834829

  11. MiRNAs in bone diseases.

    PubMed

    Moore, Benjamin T; Xiao, Peng

    2013-01-01

    MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

  12. Ventricular Septal Dissection Complicating Inferior Wall Myocardial Infarction

    PubMed Central

    Kalvin, Lindsey; Yousefzai, Rayan; Khandheria, Bijoy K.; Paterick, Timothy E.

    2017-01-01

    Postmyocardial infarction ventricular septal defect is an increasingly rare mechanical complication of acute myocardial infarction. We present a case of acute myocardial infarction from right coronary artery occlusion that developed hypotension and systolic murmur 12 hours after successful percutaneous coronary intervention. Although preoperative imaging suggested a large ventricular septal defect and a pseudoaneurysm, intraoperative findings concluded a serpiginous dissection of the ventricular septum. The imaging technicalities are discussed.

  13. The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays.

    PubMed

    Zhang, Chunyan; Bai, Nan; Huang, Wenrong; Zhang, Pengjun; Luo, Yuan; Men, Shasha; Wen, Ting; Tong, Hongli; Wang, Shuhong; Tian, Ya-Ping

    2016-10-01

    Currently, the diagnosis of acute graft-versus-host disease (aGVHD) is mainly based on clinical symptoms and biopsy results. This study was designed to further explore new no noninvasive biomarkers for aGVHD prediction/diagnosis. We profiled miRNAs in serum pools from patients with aGVHD (grades II-IV) (n = 9) and non-aGVHD controls (n = 9) by real-time qPCR-based TaqMan MicroRNA arrays. Then, predictive models were established using related miRNAs (n = 38) and verified by a double-blind trial (n = 54). We found that miR-411 was significantly down regulated when aGVHD developed and recovered when aGVHD was controlled, which demonstrated that miR-411 has potential as an indicator for aGVHD monitoring. We developed and validated a predictive model and a diagnostic model for aGVHD. The predictive model included two miRNAs (miR-26b and miR-374a), which could predict an increased risk for aGVHD 1 or 2 weeks in advance, with an AUC, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 0.722, 76.19 %, and 69.70 %, respectively. The diagnostic model included three miRNAs (miR-28-5p, miR-489, and miR-671-3p) with an AUC, PPV, and NPV of 0.841, 85.71 % and 83.33 %, respectively. Our results show that circulating miRNAs (miR-26b and miR-374a, miR-28-5p, miR-489 and miR-671-3p) may serve as biomarkers for the prediction and diagnosis of grades II-IV aGVHD.

  14. 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

  15. [LGM inferior vena cava filters--observation of 79 patients].

    PubMed

    Hajduk, B; Tomkowski, W; Fijałkowska, A; Oniszh, K; Małek, G; Wawrzyńska, L; Radomyski, A; Filipecki, S; Torbicki, A

    2000-11-01

    The aim of the study was to assess effectiveness and safety of the LGM inferior vena cava (IVC) filters in patients with venous thromboembolic disease. In the Department of Internal Medicine of Institute of Tuberculosis and Lung Diseases in Warsaw 79 LGM IVC filters have been inserted since 1993. Indications for filters placement were as follows: recurrent pulmonary embolism (pe) despite anticoagulation--17 patients (pts), severe bleeding complications of thrombolytic or anticoagulant therapy--11 pts, contraindications for thrombolytic and/or anticoagulant treatment--5 pts, massive pe--14 pts, chronic thromboembolic-major vessel pulmonary hypertension (CTEPH)--30 pts, extensive deep vein thrombosis of lower limbs or vena cava inferior in patients with urgent indications for surgery--24 pts. Each filter placement was preceded by cavography. The diagnostic procedures (mainly ultrasonography) were performed after 3-6 and 12 months in the first year then once yearly during follow-up period. Oral anticoagulants (OA) or low-molecular-weight heparins (LMWH) were instituted in the majority of patients. 58 patients are still alive, 21 patients died. Only two non-fatal episodes of recurrent pe were documented. Other complications were rare and insignificant. We have not observed excess rate of recurrent deep venous thrombosis nor thrombosis at the filter site. The LGM IVC filters are effective and safe in such selectively chosen group of patients.

  16. Monopolar intracochlear pulse trains selectively activate the inferior colliculus.

    PubMed

    Schoenecker, Matthew C; Bonham, Ben H; Stakhovskaya, Olga A; Snyder, Russell L; Leake, Patricia A

    2012-10-01

    Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

  17. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma

    PubMed Central

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Gennaro, Gianfranco Di; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-01-01

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30–50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs. PMID:27057640

  18. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma.

    PubMed

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Di Gennaro, Gianfranco; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-05-10

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30-50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs.

  19. Expression profiles of miRNAs in Gossypium raimondii *

    PubMed Central

    Ma, Jun; Guo, Teng-long; Wang, Qing-lian; Wang, Kun-bo; Sun, Run-run; Zhang, Bao-hong

    2015-01-01

    miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA molecules with 20–24 nucleotides (nt) in length that function as post-transcriptional modulators of gene expression in eukaryotic cells. Functional studies have demonstrated that plant miRNAs are involved in the regulation of a wide range of plant developmental processes. To date, however, no research has been carried out to study the expression profiles of miRNAs in Gossypium raimondii, a model cotton species. We selected 16 miRNAs to profile their tissue-specific expression patterns in G. raimondii four different tissues, and these miRNAs are reported to play important roles in plant growth and development. Our results showed that the expression levels of these miRNAs varied significantly from one to another in a tissue-dependent manner. Eight miRNAs, including miR-159, miR-162, miR-164, miR-172, miR-390, miR-395, miR-397, and miR-398, exhibited exclusively high expression levels in flower buds, suggesting that these miRNAs may play significant roles in floral development. The expression level of miR-164 was relatively high in shoots beside flower buds, implying that the function of miR-164 is not only limited to floral development but it may also play an important role in shoot development. Certain miRNAs such as miR-166 and miR-160 were extremely highly expressed in all of the four tissues tested compared with other miRNAs investigated, suggesting that they may play regulatory roles at multiple development stages. This study will contribute to future studies on the functional characterization of miRNAs in cotton. PMID:25845363

  20. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer

    PubMed Central

    Han, Ji-Guang; Jiang, Yong-Dong; Zhang, Chun-Hui; Yang, Yan-Mei; Pang, Da; Song, Yan-Ni

    2017-01-01

    Purpose Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. Methods Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. Results Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. Conclusion The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls. PMID:28203552

  1. 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

  2. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    PubMed Central

    Wang, Hom-Lay; Sabalys, Gintautas

    2011-01-01

    ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

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

    PubMed Central

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

    2012-01-01

    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 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 spatial tuning curves indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic pips. PMID:21828906

  4. 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.

  5. MiRTDL: a deep learning approach for miRNA target prediction.

    PubMed

    Cheng, Shuang; Guo, Maozu; Wang, Chunyu; Liu, Xiaoyan; Liu, Yang; Wu, Xuejian

    2015-12-22

    MicroRNAs (miRNAs) regulate genes that are associated with various diseases. To better understand miRNAs, the miRNA regulatory mechanism needs to be investigated and the real targets identified. Here, we present miRTDL, a new miRNA target prediction algorithm based on convolutional neural network (CNN). The CNN automatically extracts essential information from the input data rather than completely relying on the input dataset generated artificially when the precise miRNA target mechanisms are poorly known. In this work, the constraint relaxing method is first used to construct a balanced training dataset to avoid inaccurate predictions caused by the existing unbalanced dataset. The miRTDL is then applied to 1,606 experimentally validated miRNA target pairs. Finally, the results show that our miRTDL outperforms the existing target prediction algorithms and achieves significantly higher sensitivity, specificity and accuracy of 88.43%, 96.44% and 89.98%, respectively. We also investigate the miRNA target mechanism, and the results show that the complementation features are more important than the others.

  6. miRNA Modulation of Cholesterol Homeostasis

    PubMed Central

    Fernández-Hernando, Carlos; Moore, Kathryn J.

    2012-01-01

    Although the roles of the SREBP1 and SREBP2 transcription factors in regulating fatty acid and cholesterol synthesis and uptake have been known for some time, it was recently discovered that two related microRNAs, miR-33a and miR-33b, are embedded in these genes. Studies indicate that miR-33a and miR-33b act with their host genes, Srebp2 and Srebp1, respectively, to reciprocally regulate cholesterol homeostasis and fatty acid metabolism in a negative feedback loop. miR-33 has been shown to post-transcriptionally repress key genes involved in cellular cholesterol export and HDL metabolism (Abca1, Abcg1, Npc1), fatty acid oxidation (Crot, Cpt1a, Hadhb, Ampk), and glucose metabolism (Sirt6, Irs2). Delivery of inhibitors of miR-33 in vitro and in vivo relieves repression of these genes resulting in up-regulation of the associated metabolic pathways. In mouse models, miR-33 antagonism has proven has proven to be an effective strategy for increasing plasma HDL cholesterol and fatty acid oxidation, and protecting from atherosclerosis. These exciting findings have opened up promising new avenues for the development of therapeutics to treat dyslipidemia and other metabolic disorders. PMID:22011750

  7. Time Series miRNA-mRNA integrated analysis reveals critical miRNAs and targets in macrophage polarization

    PubMed Central

    Lu, Liangqun; McCurdy, Sara; Huang, Sijia; Zhu, Xun; Peplowska, Karolina; Tiirikainen, Maarit; Boisvert, William A.; Garmire, Lana X.

    2016-01-01

    Polarization of macrophages is regulated through complex signaling networks. Correlating miRNA and mRNA expression over time after macrophage polarization has not yet been investigated. We used paired RNA-Seq and miRNA-Seq experiments to measure the mRNA and miRNA expression in bone marrow-derived macrophages over a time-series of 8 hours. Bioinformatics analysis identified 31 differentially expressed miRNAs between M1 and M2 polarized macrophages. The top 4 M1 miRNAs (miR-155-3p, miR-155-5p, miR-147-3p and miR-9-5p) and top 4 M2 miRNAs (miR-27a-5p, let-7c-1-3p, miR-23a-5p and miR-23b-5p) were validated by qPCR. Interestingly, M1 specific miRNAs could be categorized to early- and late-response groups, in which three new miRNAs miR-1931, miR-3473e and miR-5128 were validated as early-response miRNAs. M1 polarization led to the enrichment of genes involved in immune responses and signal transduction, whereas M2 polarization enriched genes involved in cell cycle and metabolic processes. C2H2 zinc-finger family members are key targets of DE miRNAs. The integrative analysis between miRNAs and mRNAs demonstrates the regulations of miRNAs on nearly four thousand differentially expressed genes and most of the biological pathways enriched in macrophage polarization. In summary, this study elucidates the expression profiles of miRNAs and their potential targetomes during macrophage polarization. PMID:27981970

  8. 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.

  9. 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

  10. Proof-of-concept study: profile of circulating micro RNAs in bovine serum harvested during acute and persistent FMDV infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expression of 144 distinct bovine microRNAs (miRNAs) was quantified in bovine serum harvested during different phases of infection with foot-and-mouth disease virus (FMDV). There were marked differences in miRNA expression between acute, persistent, and convalescent phases of infection. During acu...

  11. Impact of microvascular obstruction on semiautomated techniques for quantifying acute and chronic myocardial infarction by cardiovascular magnetic resonance

    PubMed Central

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Weinmann, Shane; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Moon, James C; Hausenloy, Derek J

    2016-01-01

    Aims The four most promising semiautomated techniques (5-SD, 6-SD, Otsu and the full width half maximum (FWHM)) were compared in paired acute and follow-up cardiovascular magnetic resonance (CMR), taking into account the impact of microvascular obstruction (MVO) and using automated extracellular volume fraction (ECV) maps for reference. Furthermore, their performances on the acute scan were compared against manual myocardial infarct (MI) size to predict adverse left ventricular (LV) remodelling (≥20% increase in end-diastolic volume). Methods 40 patients with reperfused ST segment elevation myocardial infarction (STEMI) with a paired acute (4±2 days) and follow-up CMR scan (5±2 months) were recruited prospectively. All CMR analysis was performed on CVI42. Results Using manual MI size as the reference standard, 6-SD accurately quantified acute (24.9±14.0%LV, p=0.81, no bias) and chronic MI size (17.2±9.7%LV, p=0.88, no bias). The performance of FWHM for acute MI size was affected by the acquisition sequence used. Furthermore, FWHM underestimated chronic MI size in those with previous MVO due to the significantly higher ECV in the MI core on the follow-up scans previously occupied by MVO (82 (75–88)% vs 62 (51–68)%, p<0.001). 5-SD and Otsu were precise but overestimated acute and chronic MI size. All techniques were performed with high diagnostic accuracy and equally well to predict adverse LV remodelling. Conclusions 6-SD was the most accurate for acute and chronic MI size and should be the preferred semiautomatic technique in randomised controlled trials. However, 5-SD, FWHM and Otsu could also be used when precise MI size quantification may be adequate (eg, observational studies). PMID:28008358

  12. 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.

  13. 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.

  14. Inference of gene regulation via miRNAs during ES cell differentiation using MiRaGE method.

    PubMed

    Yoshizawa, Masato; Taguchi, Y-H; Yasuda, Jun

    2011-01-01

    MicroRNA (miRNA) is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression) method to infer the regulation of gene expression by miRNAs from changes of gene expression profiles. The method does not require precedent array normalization. We applied the method to elucidate possibly important miRNAs during embryonic stem (ES) cell differentiation to neuronal cells and we infer that certain miRNAs, including miR-200 family, miR-429, miR-302 family, and miR-17-92 cluster members may be important to the maintenance of undifferentiated status in ES cells.

  15. Effect of miR-146a and miR-155 on cardiac xenotransplantation

    PubMed Central

    Zhao, Zhicheng; Qi, Feng; Liu, Tong; Fu, Weihua

    2016-01-01

    The aim of the present study was to investigate the expression levels of miR-146a and miR-155 in a cardiac xenograft model treated with the immunosuppressant FK506, and to construct lentiviral vectors to further study the roles of miR-146a and miR-155 in cardiac xenotransplantation. Expression levels of miR-146a and miR-155 were examined by quantitative polymerase chain reaction analysis and protein expression of RelA, which is a member of the nuclear factor-κB family, was examined by western blot analysis. Pre-miR-146a and pre-miR-155 fragments were designed and synthesized according to MiRBase and were cloned into the plasmid pCDH1-MCS1-EF1-copGFP. Recombinant plasmids were identified by enzyme digestion and sequencing. Survival time of cardiac grafts in the FK506 treatment group was significantly increased in comparison with the control group (P<0.05). In addition, the histopathological grading results were significantly decreased in the treatment group (P<0.05). A significant decrease in RelA protein expression levels was observed in the treatment group (P<0.05), along with a significant increase in miR-146a expression levels (P<0.05) and a significant decrease in miR-155 expression levels (P<0.05). Digestion and sequencing findings demonstrated that the insertion of miRNA into the plasmid pCDH1-MCS1-EF1-copGFP conformed with the pre-miRNAs, and the lentiviral vectors were concentrated to a titer of 5×107 IFU/ml. These findings demonstrated that FK506 is able to inhibit the rejection effect in a mouse-to-rat cardiac xenotransplantation model. FK506 treatment altered the expression levels of miR-146a and miR-155, indicating that they may have an important role in regulating the immune response to the rejection effect. miR-146a and miR-155 lentiviral vectors were successfully constructed for further experiments both in vitro and in vivo. PMID:28101175

  16. Predictive and Prognostic Roles of Abnormal Expression of Tissue miR-125b, miR-221, and miR-222 in Glioma.

    PubMed

    Li, Xinxing; Zheng, Jihui; Chen, Liangyu; Diao, Hongyu; Liu, Yunhui

    2016-01-01

    Glioma is the most prevalent primary brain tumors in adults. In addition to the high incidence and mortality rate, the 5-year survival rate of glioma is also extremely low. MicroRNAs (miRNAs), as a class of small non-coding RNAs, may play an important role in carcinogenesis. It was also proposed that miRNAs might also be associated with glioma diagnosis and prognosis. In this study, we aimed at investigating the predictive and prognostic values of miR-125b, miR-221, and miR-222 in glioma and, hopefully, to provide some evidence for novel therapy of glioma. Tissue specimens were obtained from tumor tissue and adjacent non-tumor tissue. RNA was extracted and qRT-PCR was performed with U6 being the internal control. Receiver-operating characteristic (ROC) curves were constructed, and the area under the ROC curves (AUC) was calculated to evaluate the significance of candidate miRNAs in distinguishing glioma tumor tissues and adjacent normal tissues. Survival curves of Kaplan-Meier method were constructed for both high expression group and low expression group, and the difference between curves was evaluated by log-rank test. All the statistical analyses were performed using Stata version 12.0 software, and graphs were generated by GraphPad Prism 5.0. The significance of miR-125b, miR-221, and miR-222 expression level in distinguishing glioma tumor from adjacent non-tumor tissues was further validated. Combination of miR-125b, miR-221, and miR-22 was significantly superior compared to the clinical standard of using these miRNAs alone. A clear demarcation was shown by survival analysis between patients with high miR-125b, miR-221, and miR-222 expression and patients with poor prognosis. Similarly, panel of these miRNAs could play a better prognostic role in glioma. In this study, we confirmed the significance of miR-125b, miR-221, and miR-222 in distinguishing glioma tumor from adjacent non-tumor tissues. Higher expressions of miR-125b and miR-222 have also been proved

  17. 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

  18. miR-15 and miR-16 induce apoptosis by targeting BCL2.

    PubMed

    Cimmino, Amelia; Calin, George Adrian; Fabbri, Muller; Iorio, Marilena V; Ferracin, Manuela; Shimizu, Masayoshi; Wojcik, Sylwia E; Aqeilan, Rami I; Zupo, Simona; Dono, Mariella; Rassenti, Laura; Alder, Hansjuerg; Volinia, Stefano; Liu, Chang-Gong; Kipps, Thomas J; Negrini, Massimo; Croce, Carlo M

    2005-09-27

    Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.

  19. 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.

  20. Retrieval of Inferior Vena Cava Filters: Technical Considerations.

    PubMed

    Laws, James L; Lewandowski, Robert J; Ryu, Robert K; Desai, Kush R

    2016-06-01

    Placement of retrievable inferior vena cava filters has seen rapid growth since their introduction into clinical practice. When retrieved, these devices offer the notional benefit of temporary protection from pulmonary embolism related to lower extremity deep venous thrombosis, and mitigation of filter-related deep venous thrombosis. When promptly removed after the indication for mechanical prophylaxis is no longer present, standard endovascular retrieval techniques are frequently successful. However, the majority of these devices are left in place for extended periods of time, which has been associated with greater device-related complications when left in situ, and failure of standard techniques when retrieval is attempted. The development of advanced retrieval techniques has had a positive impact on retrieval of these embedded devices. In this article, technical considerations in the retrieval of such devices, with an emphasis on advanced techniques to facilitate retrieval of embedded devices, are discussed.

  1. Inferior vena caval filter strut perforation causing intramural duodenal haematoma

    PubMed Central

    Williams, Zoheb Berry; Organ, Nicole M.; Deane, Stephen

    2016-01-01

    We present a case of intramural duodenal haematoma caused by inferior vena caval (IVC) filter strut perforation requiring innovative open and endovascular retrieval. A 32-year-old woman presents in shock with dull epigastric pain and non-bilious vomiting. She had previously had an IVC filter for deep venous thrombosis and pulmonary embolism. Computed tomography demonstrated strut perforation into the second part of the duodenum, causing intramural haematoma and duodenal obstruction. Laparotomy facilitated evacuation of the duodenal haematoma, while the IVC filter was retrieved by endovascular means. Causes of duodenal haematoma include blunt trauma, haematologic malignancy, coagulopathy, percutaneous or endoscopic procedures, pancreatic pathology, peptic ulcer disease and aortoenteric fistula. Duodenal haematoma is rare and is usually managed conservatively or by percutaneous drainage. While this patient had a typical presentation, IVC filter strut perforation has not been described in the literature as a cause for duodenal haematoma. PMID:27887016

  2. 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.

  3. Commissural functional topography of the inferior colliculus assessed in vitro

    PubMed Central

    Lee, Charles C.; Yanagawa, Yuchio; Imaizumi, Kazuo

    2015-01-01

    The inferior colliculus (IC) receives ascending and descending information from several convergent neural sources. As such, exploring the neural pathways that converge in the IC is crucial to uncovering their multi-varied roles in the integration of auditory and other sensory information. Among these convergent pathways, the IC commissural connections represent an important route for the integration of bilateral information in the auditory system. Here, we describe the preparation and validation of a novel in vitro slice preparation for examining the functional topography and synaptic properties of the commissural and intrinsic projections in the IC of the mouse. This preparation, in combination with modern genetic approaches in the mouse, enables the specific examination of these pathways, which potentially can reveal cell-type specific processing channels in the auditory midbrain. PMID:26319767

  4. Anesthetic Efficacy of Bupivacaine Solutions in Inferior Alveolar Nerve Block

    PubMed Central

    Volpato, Maria Cristina; Ranali, José; Ramacciato, Juliana Cama; de Oliveira, Patrícia Cristine; Ambrosano, Glaúcia Maria Bovi; Groppo, Francisco Carlos

    2005-01-01

    The purpose of this study was to compare the anesthetic efficacy of 2 bupivacaine solutions. Twenty-two volunteers randomly received in a crossover, double-blinded manner 2 inferior alveolar nerve blocks with 1.8 mL of racemic bupivacaine and a mixture of 75% levobupivacaine and 25% dextrobupivacaine, both 0.5% and with 1 : 200,000 epinephrine. Before and after the injection, the first mandibular pre-molar was evaluated every 2 minutes until no response to the maximal output (80 reading) of the pulp tester and then again every 20 minutes. Data were analyzed using the Wilcoxon paired test and the paired t test. No differences were found between the solutions for onset and duration of pulpal anesthesia and duration of soft tissue anesthesia (P > .05). It was concluded that the solutions have similar anesthetic efficacy. PMID:16596912

  5. Is left inferior frontal gyrus a general mechanism for selection?

    PubMed

    Zhang, John X; Feng, Ching-Mei; Fox, Peter T; Gao, Jia-Hong; Tan, Li Hai

    2004-10-01

    Converging lines of research in neuroimaging recognize selection as one of the critical functions of prefrontal cortex (e.g., see Annu. Rev. Neurosci. 24, 2001 167). We examined a central thesis of a selection hypothesis (Neuropsychologia 41, 2003 280) that the left inferior frontal gyrus (LIFG) serves as a general mechanism for selecting among competing representations (Annu. Rev. Neurosci. 18, 1995 193). Participants were presented with two sets of letters to remember and then cued to select one set from the two as the target set for subsequent recognition. LIFG showed significantly more activation when the cue elicited a strong need for selection, relative to when it did not, suggesting that the involvement of this area in selection is generalizable beyond semantic retrieval tasks as originally found. This result provides supporting evidence for the selection hypothesis.

  6. 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. PMID:27579443

  7. Evolution of the miR-290–295/miR-371–373 Cluster Family Seed Repertoire

    PubMed Central

    Wu, Shuang; Aksoy, Munevver; Shi, Jianting; Houbaviy, Hristo Botev

    2014-01-01

    Expression of the mouse miR-290–295 cluster and its miR-371–373 homolog in human is restricted to early embryos, primordial germ cells, the germ line stem cell compartment of the adult testis and to stem cell lines derived from the early embryonic lineages. Sequencing data suggest considerable seed diversification between the seven homologous pre-miRNAs of miR-290–295 but it is not clear if all of the implied miR-290–295 seeds are also conserved in the human miR-371–373 cluster, which consists of only three homologous pre-miRNAs. By employing miRNA target reporters we show that most, if not all, seeds in miR-290–295 are represented in miR-371–373. In the mouse, pre-miR-290, pre-miR-292 and pre-miR-293 express subsets of the miRNA isoforms processed from the single human pre-miR-371. Comparison of the possible miR-290–295/miR-371–373 seed repertoires in placental mammals suggests a model for the evolution of this miRNA cluster family, which would be otherwise difficult to deduce based solely on pre-miRNA sequence comparisons. The conservation of co-expressed seeds that is characteristic of miR-290–295/miR-371–373 should be taken into account in models of the corresponding miRNA-target interaction networks. PMID:25268927

  8. Sensitivity of rat inferior colliculus neurons to frequency distributions

    PubMed Central

    Parthasarathy, Aravindakshan; Han, Emily X.; Bartlett, Edward L.

    2015-01-01

    Stimulus-specific adaptation refers to a neural response reduction to a repeated stimulus that does not generalize to other stimuli. However, stimulus-specific adaptation appears to be influenced by additional factors. For example, the statistical distribution of tone frequencies has recently been shown to dynamically alter stimulus-specific adaptation in human auditory cortex. The present study investigated whether statistical stimulus distributions also affect stimulus-specific adaptation at an earlier stage of the auditory hierarchy. Neural spiking activity and local field potentials were recorded from inferior colliculus neurons of rats while tones were presented in oddball sequences that formed two different statistical contexts. Each sequence consisted of a repeatedly presented tone (standard) and three rare deviants of different magnitudes (small, moderate, large spectral change). The critical manipulation was the relative probability with which large spectral changes occurred. In one context the probability was high (relative to all deviants), while it was low in the other context. We observed larger responses for deviants compared with standards, confirming previous reports of increased response adaptation for frequently presented tones. Importantly, the statistical context in which tones were presented strongly modulated stimulus-specific adaptation. Physically and probabilistically identical stimuli (moderate deviants) in the two statistical contexts elicited different response magnitudes consistent with neural gain changes and thus neural sensitivity adjustments induced by the spectral range of a stimulus distribution. The data show that already at the level of the inferior colliculus stimulus-specific adaptation is dynamically altered by the statistical context in which stimuli occur. PMID:26354316

  9. Electrophysiological properties of inferior olive neurons: A compartmental model.

    PubMed

    Schweighofer, N; Doya, K; Kawato, M

    1999-08-01

    As a step in exploring the functions of the inferior olive, we constructed a biophysical model of the olivary neurons to examine their unique electrophysiological properties. The model consists of two compartments to represent the known distribution of ionic currents across the cell membrane, as well as the dendritic location of the gap junctions and synaptic inputs. The somatic compartment includes a low-threshold calcium current (I(Ca_l)), an anomalous inward rectifier current (I(h)), a sodium current (I(Na)), and a delayed rectifier potassium current (I(K_dr)). The dendritic compartment contains a high-threshold calcium current (I(Ca_h)), a calcium-dependent potassium current (I(K_Ca)), and a current flowing into other cells through electrical coupling (I(c)). First, kinetic parameters for these currents were set according to previously reported experimental data. Next, the remaining free parameters were determined to account for both static and spiking properties of single olivary neurons in vitro. We then performed a series of simulated pharmacological experiments using bifurcation analysis and extensive two-parameter searches. Consistent with previous studies, we quantitatively demonstrated the major role of I(Ca_l) in spiking excitability. In addition, I(h) had an important modulatory role in the spike generation and period of oscillations, as previously suggested by Bal and McCormick. Finally, we investigated the role of electrical coupling in two coupled spiking cells. Depending on the coupling strength, the hyperpolarization level, and the I(Ca_l) and I(h) modulation, the coupled cells had four different synchronization modes: the cells could be in-phase, phase-shifted, or anti-phase or could exhibit a complex desynchronized spiking mode. Hence these simulation results support the counterintuitive hypothesis that electrical coupling can desynchronize coupled inferior olive cells.

  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. GUSTO V: combination drug treatment of acute myocardial infarction. Global Use of Strategies to Open Occluded Coronary Arteries.

    PubMed

    Askari, Arman T; Lincoff, A Michael

    2002-07-01

    The combination of abciximab in full doses and reteplase in half doses did not significantly reduce the rate of mortality at 30 days in patients with acute ST-segment elevation myocardial infarction (MI) when compared with reteplase in full doses in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO V) trial. However, subgroup analysis indicates that the combined regimen reduced the complications of acute MI, representing an important alternative strategy for pharmacologic reperfusion.

  12. 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

  13. Using miRNA-Analyzer for the Analysis of miRNA Data

    PubMed Central

    Guzzi, Pietro Hiram; Tradigo, Giuseppe; Veltri, Pierangelo

    2016-01-01

    MicroRNAs (miRNAs) are small biological molecules that play an important role during the mechanisms of protein formation. Recent findings have demonstrated that they act as both positive and negative regulators of protein formation. Thus, the investigation of miRNAs, i.e., the determination of their level of expression, has developed a huge interest in the scientific community. One of the leading technologies for extracting miRNA data from biological samples is the miRNA Affymetrix platform. It provides the quantification of the level of expression of the miRNA in a sample, thus enabling the accumulation of data and allowing the determination of relationships among miRNA, genes, and diseases. Unfortunately, there is a lack of a comprehensive platform able to provide all the functions needed for the extraction of information from miRNA data. We here present miRNA-Analyzer, a complete software tool providing primary functionalities for miRNA data analysis. The current version of miRNA-Analyzer wraps the Affymetrix QCTool for the preprocessing of binary data files, and then provides feature selection (the filtering by species and by the associated p-value of preprocessed files). Finally, preprocessed and filtered data are analyzed by the Multiple Experiment Viewer (T-MEV) and Short Time Series Expression Miner (STEM) tools, which are also wrapped into miRNA-Analyzer, thus providing a unique environment for miRNA data analysis. The tool offers a plug-in interface so it is easily extensible by adding other algorithms as plug-ins. Users may download the tool freely for academic use at https://sites.google.com/site/mirnaanalyserproject/d. PMID:27983673

  14. miRsig: a consensus-based network inference methodology to identify pan-cancer miRNA-miRNA interaction signatures

    PubMed Central

    Nalluri, Joseph J.; Barh, Debmalya; Azevedo, Vasco; Ghosh, Preetam

    2017-01-01

    Decoding the patterns of miRNA regulation in diseases are important to properly realize its potential in diagnostic, prog- nostic, and therapeutic applications. Only a handful of studies computationally predict possible miRNA-miRNA interactions; hence, such interactions require a thorough investigation to understand their role in disease progression. In this paper, we design a novel computational pipeline to predict the common signature/core sets of miRNA-miRNA interactions for different diseases using network inference algorithms on the miRNA-disease expression profiles; the individual predictions of these algorithms were then merged using a consensus-based approach to predict miRNA-miRNA associations. We next selected the miRNA-miRNA associations across particular diseases to generate the corresponding disease-specific miRNA-interaction networks. Next, graph intersection analysis was performed on these networks for multiple diseases to identify the common signature/core sets of miRNA interactions. We applied this pipeline to identify the common signature of miRNA-miRNA inter- actions for cancers. The identified signatures when validated using a manual literature search from PubMed Central and the PhenomiR database, show strong relevance with the respective cancers, providing an indirect proof of the high accuracy of our methodology. We developed miRsig, an online tool for analysis and visualization of the disease-specific signature/core miRNA-miRNA interactions, available at: http://bnet.egr.vcu.edu/miRsig. PMID:28045122

  15. Universal MI definition update for cardiovascular disease.

    PubMed

    White, Harvey; Thygesen, Kristian; Alpert, Joseph S; Jaffe, Allan

    2014-01-01

    The new third universal definition of myocardial infarction (MI) is based on troponin elevation together with ischemic symptoms, ischemic ECG changes, and imaging evidence. MIs are classified into five types as to whether they are spontaneous, secondary to imbalance between coronary artery blood supply and demand, related to sudden death, or related to revascularization procedures. The definition is based on a rise and/or fall in troponin levels occurring in a clinical setting. There have been modifications over previous definitions with adding intracoronary thrombus as a criterion, adding a new type of MI type 4c, and raising the cutpoint for the diagnosis of MI related to percutaneous coronary intervention to five times the 99(th) percentile upper reference limit and requiring evidence of ischemia or angiographic complications. In clinical practice, trials, and registries, different definitions are used. There is a need for consistency with regard to the definition of MI and the universal definition should be implemented.

  16. 78 FR 15796 - Michigan Disaster #MI-00038.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Michigan Disaster MI-00038. AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... adversely affected by the disaster: Primary Counties: Mecosta. Contiguous Counties: Michigan:...

  17. Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia

    PubMed Central

    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

    2015-01-01

    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

  18. 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.

  19. Interruption of the inferior vena cava with azygos termination associated with congenital absence of portal vein.

    PubMed

    Le Borgne, J; Paineau, J; Hamy, A; Dupas, B; Lerat, F; Raoul, S; Hamel, A; Robert, R; Armstrong, O; Rogez, J M

    2000-01-01

    The authors report an exceptional and well-documented case of interruption of the retrohepatic segment of the inferior vena cava with an "azygos continuation", combined with absence of the portal vein. The only known combination of congenital anomalies of the inferior vena cava and the portal vein was that of an "azygos continuation" and a preduodenal portal vein. The double interruption, portal and inferior caval, may be associated with a disturbance of preferential flows induced by the left umbilical thrust. According to hemodynamic theory, the left umbilical flow is the determining factor in organogenesis of the portal vein and the retrohepatic segment of the inferior vena cava.

  20. 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.

  1. The NuMI neutrino beam

    DOE PAGES

    Adamson, P.; Anderson, K.; Andrews, M.; ...

    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.

  2. 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

  3. 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

  4. 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.

  5. miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico

    PubMed Central

    Barta, Tomas; Peskova, Lucie; Hampl, Ales

    2016-01-01

    MicroRNA (miRNA) sponges are RNA transcripts containing multiple high-affinity binding sites that associate with and sequester specific miRNAs to prevent them from interacting with their target messenger (m)RNAs. Due to the high specificity of miRNA sponges and strong inhibition of target miRNAs, these molecules have become increasingly applied in miRNA loss-of-function studies. However, improperly designed sponge constructs may sequester off-target miRNAs; thus, it has become increasingly important to develop a tool for miRNA sponge construct design and testing. In this study, we introduce microRNA sponge generator and tester (miRNAsong), a freely available web-based tool for generation and in silico testing of miRNA sponges. This tool generates miRNA sponge constructs for specific miRNAs and miRNA families/clusters and tests them for potential binding to miRNAs in selected organisms. Currently, miRNAsong allows for testing of sponge constructs in 219 species covering 35,828 miRNA sequences. Furthermore, we also provide an example, supplemented with experimental data, of how to use this tool. Using miRNAsong, we designed and tested a sponge for miR-145 inhibition, and cloned the sequence into an inducible lentiviral vector. We found that established cell lines expressing miR-145 sponge strongly inhibited miR-145, thus demonstrating the usability of miRNAsong tool for sponge generation. URL: http://www.med.muni.cz/histology/miRNAsong/. PMID:27857164

  6. miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico.

    PubMed

    Barta, Tomas; Peskova, Lucie; Hampl, Ales

    2016-11-18

    MicroRNA (miRNA) sponges are RNA transcripts containing multiple high-affinity binding sites that associate with and sequester specific miRNAs to prevent them from interacting with their target messenger (m)RNAs. Due to the high specificity of miRNA sponges and strong inhibition of target miRNAs, these molecules have become increasingly applied in miRNA loss-of-function studies. However, improperly designed sponge constructs may sequester off-target miRNAs; thus, it has become increasingly important to develop a tool for miRNA sponge construct design and testing. In this study, we introduce microRNA sponge generator and tester (miRNAsong), a freely available web-based tool for generation and in silico testing of miRNA sponges. This tool generates miRNA sponge constructs for specific miRNAs and miRNA families/clusters and tests them for potential binding to miRNAs in selected organisms. Currently, miRNAsong allows for testing of sponge constructs in 219 species covering 35,828 miRNA sequences. Furthermore, we also provide an example, supplemented with experimental data, of how to use this tool. Using miRNAsong, we designed and tested a sponge for miR-145 inhibition, and cloned the sequence into an inducible lentiviral vector. We found that established cell lines expressing miR-145 sponge strongly inhibited miR-145, thus demonstrating the usability of miRNAsong tool for sponge generation. URL: http://www.med.muni.cz/histology/miRNAsong/.

  7. Aberrant miRNA profiles associated with chronic benzene poisoning.

    PubMed

    Bai, Wenlin; Chen, Yujiao; Yang, Jing; Niu, Piye; Tian, Lin; Gao, Ai

    2014-06-01

    Chronic occupational benzene exposure is associated with an increased risk of hematological malignancies. To gain an insight into the new biomarkers and molecular mechanisms of chronic benzene poisoning, miRNA profiles and mRNA expression pattern from the peripheral blood mononuclear cells of chronic benzene poisoning patients and health controls matched age and gender without benzene exposure were performed using the Exiqon miRNA PCR ARRAY and Gene Chip Human Gene 2.0ST Arrays, respectively. Totally, 6 up-regulated miRNAs (miR-34a, miR-205, miR-10b, let-7d, miR-185 and miR-423-5p-2) and 7 down-regulated miRNAs (miR-133a, miR-543, hsa-miR-130a, miR-27b,miR-223, miR-142-5p and miR-320b) were found in chronic benzene poisoning group compared to health controls (P ≤ 0.05). By integrating miRNA and mRNA expression data, these differential miRNAs were mainly involved in regulation of transcription from RNA polymerase II promoter, axon guidance, regulation of transcription, DNA-dependent, nervous system development, and regulation of actin cytoskeleton organization. Further, pathway analysis indicated that SMAD4, PLCB1, NFAT5, GNAI2, PTEN, VEGFA, BCL2, CTNNB1 and CCND1 were key target genes of differential miRNAs which were implicated in Adherens junction, TGF-beta signaling pathway, Wnt signaling pathway, tight junction and Pathways in cancer. In conclusion, the aberrant miRNAs might be a potential biomarker of chronic benzene poisoning.

  8. Telomere Length, TERT, and miRNA Expression

    PubMed Central

    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

  9. miR-17, miR-21, and miR-143 Enhance Adipogenic Differentiation from Porcine Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    An, Xinglan; Ma, Kuiying; Zhang, Zhiren; Zhao, Tianchuang; Zhang, Xueming; Tang, Bo; Li, Ziyi

    2016-08-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation abilities toward adipocytes and osteoblasts. Recently, numerous studies have focused on the roles of microRNAs (miRNAs) in the process of adipogenic differentiation of human and mouse cells. However, the role of miRNAs in adipogenic differentiation process of porcine BMSCs (pBMSCs) remains unclear. In this study, pBMSCs were induced to differentiate into adipocytes using a chemical approach, and the roles of miR-17, miR-21, and miR-143 in this process were investigated. Our results showed that pBMSCs could be chemically induced to differentiate into adipocytes and that the expression of miR-17, miR-21, and miR-143 increased during differentiation. Then, overexpression of mimics of miR-17, miR-21, and miR-143 increased the number of oil red O-positive cells of adipocyte differentiation. The expression levels of CCAAT/enhancer-binding protein alpha (C/EBPα) mRNA showed increases of 1.8-, 1.5-, and 1.2-fold in the groups expressing mimics of miR-21, miR-17, and miR-143, respectively, at day 20. These results demonstrate that miR-17, miR-21, and miR-143 are involved in and promote the adipogenic differentiation of pBMSCs. This study provides an experimental basis for establishing a stable and efficient adipogenic differentiation model for applications in cell therapy and tissue engineering.

  10. miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells.

    PubMed

    Naqvi, Afsar Raza; Fordham, Jezrom B; Nares, Salvador

    2015-02-15

    Micro-RNAs (miRNAs) are small noncoding RNAs that regulate various biological pathways. As their role in phagocytosis remains poorly understood, we investigated their impact on phagocytosis in myeloid inflammatory cells. Seven miRNAs (miR-24, -30b, -101, 142-3p, -652-3p, -652-5p, and -1275) that were differentially expressed during monocyte to macrophage (Mφ) and monocyte to dendritic cell (DC) differentiation were screened for their potential role in phagocytosis. Among these, overexpression of miR-24, miR-30b, and miR-142-3p in human monocyte-derived Mφ, DC, monocytes, and PBMCs significantly attenuate phagocytosis of Escherichia coli and Staphylococcus aureus, as well as the secretion of inflammatory mediators, including TNF-α, IL-6, and IL-12p40. miRNA-mediated changes in cytokine profiles were observed at transcriptional and/or posttranscriptional levels and importantly exhibit miRNA-specific impact. To examine the underlying mechanism, we monitored the expression of phagocytosis pathway-associated genes and identified several genes that were altered in Mφ and DC transfected with miR-24, miR-30b, and miR-142-3p mimics. Some of these genes with altered expression also harbor putative miRNA binding sites. We show that miR-142-3p directly regulates protein kinase Cα (PKCα), a key gene involved in phagocytosis. Interestingly, miR-142-3p and PKCα exhibit antagonistic expression during Mφ and DC differentiation. Short interfering RNA-mediated knockdown of PKCα in Mφ leads to reduced bacterial uptake, further highlighting the role of the gene in phagocytosis. Overall, these results demonstrate that miR-24, miR-30b, and miR-142-3p regulate phagocytosis and associated cytokine production in myeloid inflammatory cells through modulation of various genes involved in the pathway.

  11. miRNAs associated with immune response in teleost fish.

    PubMed

    Andreassen, Rune; Høyheim, Bjørn

    2017-02-28

    MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes

  12. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives.

    PubMed

    Aqeilan, R I; Calin, G A; Croce, C M

    2010-02-01

    MicroRNAs (miRNAs) encoded by the miR-15/16 cluster are known to act as tumor suppressors. Expression of these miRNAs inhibits cell proliferation, promotes apoptosis of cancer cells, and suppresses tumorigenicity both in vitro and in vivo. miR-15a and miR-16-1 function by targeting multiple oncogenes, including BCL2, MCL1, CCND1, and WNT3A. Down-regulation of these miRNAs has been reported in chronic lymphocytic lymphoma (CLL), pituitary adenomas, and prostate carcinoma. This review summarizes the discovery, functions, and clinical relevance of these miRNAs in cancer, particularly CLL.

  13. microRNA function is limited to cytokine control in the acute response to virus infection

    PubMed Central

    Aguado, Lauren C.; Schmid, Sonja; Sachs, David; Shim, Jaehee V.; Lim, Jean K.; tenOever, Benjamin R.

    2015-01-01

    SUMMARY With the capacity to fine-tune protein expression via sequence-specific interactions, microRNAs (miRNAs) help regulate cell maintenance and differentiation. While some studies have also implicated miRNAs as regulators of the antiviral response, others have found that the RISC complex that facilitates miRNA-mediated silencing is rendered non-functional during cellular stress, including virus infection. To determine the global role of miRNAs in the cellular response to virus infection, we generated a vector that rapidly eliminates total cellular miRNA populations in terminally differentiated primary cultures. Loss of miRNAs has a negligible impact on both innate sensing of and immediate response to acute viral infection. In contrast, miRNA depletion specifically enhances cytokine expression, providing a post-translational mechanism for immune cell activation during cellular stress. This work highlights the physiological role of miRNAs during the antiviral response and suggests their contribution is limited to chronic infections and the acute activation of the adaptive immune response. PMID:26651947

  14. Breast-feeding after inferior pedicle reduction mammaplasty.

    PubMed

    Brzozowski, D; Niessen, M; Evans, H B; Hurst, L N

    2000-02-01

    The breast-feeding practices of a series of postpartum women, who had undergone prior reduction mammaplasty by means of an inferior pedicle approach, are reported in this retrospective study. Also identified are the factors that influenced the decision to breast-feed postoperatively. From a patient pool of 544 individuals who elected to have reduction mammaplasty between 1984 and 1994 (age range, 15 to 35 years), 334 could be contacted and interviewed by means of telephone by using a standardized questionnaire. Successful breast-feeding was defined as the ability to feed for a duration equal to or greater than 2 weeks. Seventy-eight patients had children after their breast reduction surgery. Fifteen of the 78 patients (19.2 percent) breast-fed exclusively, 8 (10.3 percent) breast-fed with formula supplementation, 14 (17.9 percent) had an unsuccessful breast-feeding attempt, and 41 (52.6 percent) did not attempt breast-feeding. Of the 41 patients not attempting to breast-feed, 9 patients did so as a direct consequence of discouragement by a health care professional. Further reasons for feeding with supplementation, having an unsuccessful attempt, and not attempting to breast-feed are presented. Of the 78 women who had children postoperatively, a total of 27 were discouraged from breast-feeding by medical professionals with only 8 of the 27 (29.6 percent) subsequently attempting, despite this recommendation. In comparison, 26 patients were encouraged to breast-feed; nineteen (73.1 percent) of them did subsequently attempt breast-feeding. This rate is statistically significant by using a chi2 test with 1 df(p = 0.0016). Postpartum breast engorgement and lactation was experienced by 31 of the 41 patients not attempting to breast-feed. Of these 31 patients, 19 believed that they would have been able to breast-feed due to the extent of breast engorgement and lactation experienced. Given the use of an inferior flap mammaplasty technique and patient encouragement, the

  15. 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.

  16. Centrality-Dependent Modification of Jet-Production Rates in Deuteron-Gold Collisions at <mi>smi><mi>Nmi><mi>N>=200 <mi>GeV>

    SciTech Connect

    Adare, A.

    2016-03-24

    We measured jet production rates in p+p and d+Au collisions at <mi>smi><mi>Nmi><mi>N>=200 <mi>GeV> recorded in 2008 with the PHENIX detector at the Relativistic Heavy Ion Collider. Jets are reconstructed using the R=0.3 anti-kt algorithm from energy deposits in the electromagnetic calorimeter and charged tracks in multiwire proportional chambers, and the jet transverse momentum (pT) spectra are corrected for the detector response. Spectra are reported for jets with 12T<50 GeV/c, within a pseudorapidity acceptance of |η|<0.3. The nuclear-modification factor (RdAu) values for 0%–100% d+Au events are found to be consistent with unity, constraining the role of initial state effects on jet production. Nonetheless, the centrality-selected RdAu values and central-to-peripheral ratios (RCP) show large, pT-dependent deviations from unity, challenging the conventional models that relate hard-process rates and soft-particle production in collisions involving nuclei.

  17. miReader: Discovering Novel miRNAs in Species without Sequenced Genome

    PubMed Central

    2013-01-01

    Along with computational approaches, NGS led technologies have caused a major impact upon the discoveries made in the area of miRNA biology, including novel miRNAs identification. However, to this date all microRNA discovery tools compulsorily depend upon the availability of reference or genomic sequences. Here, for the first time a novel approach, miReader, has been introduced which could discover novel miRNAs without any dependence upon genomic/reference sequences. The approach used NGS read data to build highly accurate miRNA models, molded through a Multi-boosting algorithm with Best-First Tree as its base classifier. It was comprehensively tested over large amount of experimental data from wide range of species including human, plants, nematode, zebrafish and fruit fly, performing consistently with >90% accuracy. Using the same tool over Illumina read data for Miscanthus, a plant whose genome is not sequenced; the study reported 21 novel mature miRNA duplex candidates. Considering the fact that miRNA discovery requires handling of high throughput data, the entire approach has been implemented in a standalone parallel architecture. This work is expected to cause a positive impact over the area of miRNA discovery in majority of species, where genomic sequence availability would not be a compulsion any more. PMID:23805282

  18. Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells

    PubMed Central

    Meng, Lingyu; Liu, Cuicui; Lü, Jinhui; Zhao, Qian; Deng, Shengqiong; Wang, Guangxue; Qiao, Jing; Zhang, Chuyi; Zhen, Lixiao; Lu, Ying; Li, Wenshu; Zhang, Yuzhen; Pestell, Richard G.; Fan, Huiming; Chen, Yi-Han; Liu, Zhongmin; Yu, Zuoren

    2017-01-01

    MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed ‘small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA–RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30–50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes. PMID:28045030

  19. Comprehensive expression analysis of miRNA in breast cancer at the miRNA and isomiR levels.

    PubMed

    Wu, Xianjin; Zeng, Rong; Wu, Shaoke; Zhong, Jixin; Yang, Lawei; Xu, Junfa

    2015-02-25

    Breast cancer (BC) is the main factor that leads cause of cancer death in women worldwide. A class of small non-coding RNAs, microRNAs (miRNAs), has been widely studied in human cancers as crucial regulatory molecule. Recent studies indicate that a series of isomiRs can be yielded from a miRNA locus, and these physiological miRNA isoforms have versatile roles in miRNA biogenesis. Herein, we performed a comprehensive analysis of miRNAs at the miRNA and isomiR levels in BC using next-generation sequencing data from The Cancer Genome Atlas (TCGA). Abnormally expressed miRNA (miR-21, miR-221, miR-155, miR-30e and miR-25) and isomiR profiles could be obtained at the miRNA and isomiR levels, and similar biological roles could be detected. IsomiR expression profiles should be further concerned, and especially isomiRs are actual regulatory molecules in the miRNA-mRNA regulatory networks. The study provides a comprehensive expression analysis at the miRNA and isomiR levels in BC, which indicates biological roles of isomiRs.

  20. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

    PubMed Central

    Danza, Katia; Silvestris, Nicola; Simone, Giovanni; Signorile, Michele; Saragoni, Luca; Brunetti, Oronzo; Monti, Manlio; Mazzotta, Annalisa; De Summa, Simona; Mangia, Anita; Tommasi, Stefania

    2016-01-01

    ABSTRACT 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

  1. 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

    2016-04-02

    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.

  2. 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.

  3. Serum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients.

    PubMed

    Jeanson-Leh, Laurence; Lameth, Julie; Krimi, Soraya; Buisset, Julien; Amor, Fatima; Le Guiner, Caroline; Barthélémy, Inès; Servais, Laurent; Blot, Stéphane; Voit, Thomas; Israeli, David

    2014-11-01

    Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.

  4. 75 FR 9228 - Draft Guidance for Industry on Non-Inferiority Clinical Trials; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... ``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 Trials... clinical trials. It does not create or confer any rights for or on any person and does not operate to...

  5. 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…

  6. 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.

  7. 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.…

  8. Simultaneous paresthesia of the lingual nerve and inferior alveolar nerve caused by a radicular cyst.

    PubMed

    Hamada, Yoshiki; Yamada, Hiroyuki; Hamada, Akiko; Kondoh, Toshirou; Suzuki, Mami; Noguchi, Kazuhide; Ito, Ko; Seto, Kanichi

    2005-10-01

    The inferior alveolar nerve is sometimes affected by periapical pathoses and mandibular cysts. However, mandibular intraosseous lesions have not been reported to disturb the lingual nerve. A case of simultaneous paresthesia of the right lingual nerve and the right inferior alveolar nerve is presented. The possible mechanisms of this extremely uncommon condition are discussed.

  9. 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

  10. Acute ST Elevation Myocardial Infarction in Patients With Immune Thrombocytopenia Purpura: A Case Report

    PubMed Central

    Dhillon, Sandeep K; Lee, Edwin; Fox, John; Rachko, Maurice

    2011-01-01

    Acute myocardial infarction (AMI) in patients with immune thrombocytopenic purpura (ITP) is rare. We describe a case of AMI in patient with ITP. An 81-year-old woman presented with acute inferoposterior MI with low platelet count on admission (34,000/µl). Coronary angiography revealed significant mid right coronary artery (RCA) stenosis with thrombus, subsequently underwent successful percutaneous coronary intervention (PCI). In some patients with immune thrombocytopenia purpura and acute myocardial infarction, percutaneous coronary intervention is a therapeutic option.

  11. Supra Hepatic Inferior Vena Cava Thrombosis–Surgical Challenges

    PubMed Central

    Ramamurthy, Anand; Gopashetty, Mahesh; Vijayshankar, Cuddalore Sadasivam; Khakhar, Anand

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a chronic affliction characterized by numerous liver and kidney cysts. There is a gradual but progressive renal and liver impairment which may require combined liver-kidney transplantation. Compression of the retrohepatic Inferior Vena Cava (IVC) by an enlarged polycystic liver may impede clear visualization on pre-operative imaging and miss an underlying thrombosis or obliteration. This may result in an intra-operative surprise. Management can be challenging requiring modification of conventional surgical approach. We present our experience of a 67-year-old patient who underwent combined liver-kidney deceased donor transplantation for decompensated chronic liver disease with chronic kidney disease due to ADPKD. She was diagnosed with ADPKD for 16 year, with progressive deterioration in kidney function over the last 6 year and liver decompensation following knee replacement surgery requiring regular renal replacement therapy. We report this case to highlight the peri-operative challenges and their management along with a review of published literature on this uncommon occurrence. PMID:28208936

  12. 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

  13. Obstruction increases activation in the right inferior frontal gyrus.

    PubMed

    Liu, Tao; Saito, Hirofumi; Oi, Misato

    2016-01-01

    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.

  14. 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.

  15. 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

  16. 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

  17. Skeletal stability after inferior maxillary repositioning without interpositional graft.

    PubMed

    Santos, S E; Moreira, R W F; de Moraes, M; Asprino, L; Araujo, M M

    2012-04-01

    True vertical maxillary deficiency is a characteristic of short face syndrome. In these patients, inferior repositioning of the maxilla (IRM) is indicated to improve facial aesthetics and function, but this procedure has been described as the most unstable. The aim of this study was to evaluate the long term, post surgical stability of IRM, fixed with four 2.0mm L-shaped miniplates, without any type of graft. A cephalometric study was performed, analysing linear measurements (anterior nasal spine, the A point, top of the incisor, top of the buccal-mesial cusp of the first molar, and posterior nasal spine on an X-Y coordinate system) traced immediately preoperatively, immediately postoperatively and at least 6 months post operatively. Eight young adult patients who underwent IRM were studied. The average results of this study were: surgical movement of 4.65 mm at I point, 5.32 mm at anterior nasal spine (ANS) point, and 4.70 mm at A point and relapses of 1.60 mm (35%), 2.23 mm (43%) and 2.10 mm (46%), respectively. It was concluded, that IRM using this type of internal rigid fixation without graft is unstable.

  18. [RADICAL LAPAROSCOPIC NEPHRECTOMY WITH INFERIOR VENA CAVA THROMBECTOMY].

    PubMed

    Perlin, D V; Aleksandrov, I V; Zipunnikov, V P; Ljaljuev, A M

    2015-01-01

    Laparoscopic radical nephrectomy has proven itself as the "gold standard" treatment of renal cell carcinoma. Inferior vena cava (IVC) tumor thrombus is a complicating factor that occurs in 5% to 10% of patients with renal cell carcinoma. In world literature, there are only anecdotal reports on using laparoscopic approach for IVC thrombectomy in patients with renal cell carcinoma. Herein we report our experience of laparoscopic radical nephrectomy and thrombectomy of the level II tumor thrombus in the IVC. Two patients (79-year-old female and 48-year-old male) underwent radical nephrectomy with thrombectomy from IVC for renal cell carcinoma T3bNxM0 complicated by the formation of a tumor thrombus in the IVC. To do this, IVC was isolated, the right gonadal and lumbar veins were ligated and transected. The IVC and the left renal vein blood flow were controlled with a plastic clip and Satinski clamp. After thrombectomy and resection of the IVC, the wall the defect was sutured with continuous Prolene suture. Laparoscopic radical nephrectomy with thrombectomy without conversion to open surgery was successfully carried out in both patients. During 6-18 months follow-up no local recurrence or distant metastasis were observed. Laparoscopic radical nephrectomy with thrombectomy for renal cell carcinoma complicated with tumor thrombus level II is a safe and reproducible method, which can be applied to a specific population of patients.

  19. Responses of inferior colliculus neurons to double harmonic tones.

    PubMed

    Sinex, Donal G; Li, Hongzhe

    2007-12-01

    The auditory system can segregate sounds that overlap in time and frequency, if the sounds differ in acoustic properties such as fundamental frequency (f0). However, the neural mechanisms that underlie this ability are poorly understood. Responses of neurons in the inferior colliculus (IC) of the anesthetized chinchilla were measured. The stimuli were harmonic tones, presented alone (single harmonic tones) and in the presence of a second harmonic tone with a different f0 (double harmonic tones). Responses to single harmonic tones exhibited no stimulus-related temporal pattern, or in some cases, a simple envelope modulated at f0. Responses to double harmonic tones exhibited complex slowly modulated discharge patterns. The discharge pattern varied with the difference in f0 and with characteristic frequency. The discharge pattern also varied with the relative levels of the two tones; complex temporal patterns were observed when levels were equal, but as the level difference increased, the discharge pattern reverted to that associated with single harmonic tones. The results indicated that IC neurons convey information about simultaneous sounds in their temporal discharge patterns and that the patterns are produced by interactions between adjacent components in the spectrum. The representation is "low-resolution," in that it does not convey information about single resolved components from either individual sound.

  20. 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.

  1. Complications of orthognathic surgery: the inferior alveolar nerve.

    PubMed

    D'Agostino, Antonio; Trevisiol, Lorenzo; Gugole, Fabio; Bondí, Vincenzo; Nocini, Pier Francesco

    2010-07-01

    This study analyzes permanent paresthetic disorders regarding the inferior alveolar nerve (IAN) after mandibular ramus sagittal osteotomy procedures. Fifty patients (ie, 100 nerves) who underwent mandibular bilateral sagittal split osteotomy between 2003 and 2007 were evaluated to detect sensorial disorders of the IAN. The evaluation was performed for each patient at least 1 year after surgical intervention. The sagittal osteotomy of the mandible ramus was performed according to Epker-Hunsuk technique. The method of fixing through titanium plates and monocortical screws and the displacement width of the osteotomized stumps were also considered. The evaluation of the IAN functionality was performed both subjectively, by means of a questionnaire, and clinically, by using 4 types of tests: light-touch sensation, pinprick sensation, Weber test, and Dellon test.The clinical test analysis revealed that no nervous lesion was detected in 52% of the tested sites, whereas 24% reported significant nervous lesions. In the subjective evaluations, 74% of the patients described the discomfort related to the neurologic alteration as "absent to mild" or "mild to moderate," 10% as "moderate to serious," and 4% as "serious."We observe that the percentage of significant nervous lesions is relatively low and that it matches the mean described in literature. The central nervous system capacity to hide or compensate for functional deficits due to peripheral nervous lesions was confirmed by the comparison between the results of the clinical tests and the patients' subjective evaluations.

  2. 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.

  3. Histological examination of the human obliquus capitis inferior myodural bridge.

    PubMed

    Pontell, Matthew E; Scali, Frank; Enix, Dennis E; Battaglia, Patrick J; Marshall, Ewarld

    2013-12-01

    This study was designed to examine the anatomical relationship between the obliquus capitis inferior (OCI) muscle and the cervical dura mater at the histological level. Eight human cadavers, with an average age of 65 ± 7.9 years were selected from a convenience sample for suboccipital dissection. Twelve OCI muscle specimens were excised, 100% of which emitted grossly visible soft tissue tracts that inserted into the posterolateral aspect of the cervical dura. These 12 myodural specimens were excised as single, continuous structures and sent for H&E staining. One sample also underwent immuno-peroxidase staining. Microscopic evaluation confirmed a connective tissue bridge emanating from the OCI muscular body and attaching to the posterolateral aspect of the cervical dura mater in 75% of the specimens. Microtome slices of the remaining 25% were not able to capture muscle, connective tissue and dura within the same plane and were therefore unable to be properly analyzed. The sample sent for neuro-analysis stained positively for several neuronal fascicles traveling within, and passing through the OCI myodural bridge. This study histologically confirms the presence of a connective tissue bridge that links the OCI muscle to the dura mater and the presence of neuronal tissue within this connection warrants further examination. This structure may represent a component of normal human anatomy. In addition to its hypothetical role in human homeostasis, it may contribute to certain neuropathological conditions, as well.

  4. Anterior Inferior Iliac Spine (AIIS) and Subspine Hip Impingement

    PubMed Central

    Carton, Patrick; Filan, David

    2016-01-01

    Summary Background Abnormal morphology of the anterior inferior iliac spine (AIIS) and the subspine region of the acetabular rim are increasingly being recognised as a source of symptomatic extra-articular hip impingement. This review article aims to highlight important differences in the pathogenesis, clinical presentation and management of extra-articular hip impingement from both the AIIS and subspine bony regions, and the outcome following surgical intervention. Methods A literature review was undertaken to examine the supporting evidence for AIIS and subspine hip impingement. A narrative account of the Author’s professional experience in this area, including operative technique for arthroscopic correction, is also presented. Results Abnormal morphology of the AIIS and subspine region has been classified using cadaveric, radiological and arthroscopic means; the clinical presentation and operative treatment has been documented in several case series studies. Dual pathology is often present - recognition and treatment of both intra- and extra-articular components are necessary for good postoperative outcome. Conclusions AIIS and sub-spine hip impingement should be considered as distinct pathological entities, which may also co-exist. Symptom relief can be expected following arthroscopic deformity correction with the treatment of concomitant intra-articular pathology. Failure to recognise and treat the extra-articular component may affect postoperative outcome. Level of evidence V. PMID:28066737

  5. Neurohistological examination of the inferior glenohumeral ligament of the shoulder.

    PubMed

    Steinbeck, Jörn; Brüntrup, Jens; Greshake, Oliver; Pötzl, Wolfgang; Filler, Timm; Liljenqvist, Ulf

    2003-03-01

    The neural histology of the anterior band of the inferior glenohumeral ligament (IGHL) was studied in 11 fresh shoulder specimen using a special silver impregnation technique. Between the collagen fibers small myelinated and unmyelinated dendrites could be detected. The appearance of neurovascular structures in the adjacent synovial layer clearly exceeded the typical supply to soft tissues. Analysing about 11,000 sections Ruffini mechanoreceptors that are known to be slow adapting were found on the humeral insertion of the band. The sections containing these neural end organs were identified by means of transillumination and reflection-contrast microscopy and reconstructed using three-dimensional image processing. The presence of neural structures including Ruffini corpuscles in these most important passive stabilizers of the shoulder joint shows that these ligaments function also as an active safety device. There slow adaption is a prerequisite for muscular reflexes counteracting the tensile stresses to which the passive stabilizing structures of the shoulder are exposed. A disruption of the continuity of these structures by mechanical forces or surgery can reduce the biofeedback and proprioceptive quality and thus lead to a decrease of shoulder function and/or stability. These observations should be taken into account when planning surgical interventions involving the IGHL. Procedures like capsule shifts or plications may affect mechanoreceptor orientation and concentrations, thereby affecting the interaction between these structures and the synergistic muscles. When possible, these intervention should avoid receptor-dense regions while attempting to restore normal anatomical orientation and tissue tension.

  6. Predictions Shape Confidence in Right Inferior Frontal Gyrus.

    PubMed

    Sherman, Maxine T; Seth, Anil K; Kanai, Ryota

    2016-10-05

    It is clear that prior expectations shape perceptual decision-making, yet their contribution to the construction of subjective decision confidence remains largely unexplored. We recorded fMRI data while participants made perceptual decisions and confidence judgments, manipulating perceptual prior expectations while controlling for potential confounds of attention. Results show that subjective confidence increases as expectations increasingly support the decision, and that this relationship is associated with BOLD activity in right inferior frontal gyrus (rIFG). Specifically, rIFG is sensitive to the discrepancy between expectation and decision (mismatch), and higher mismatch responses are associated with lower decision confidence. Connectivity analyses revealed expectancy information to be represented in bilateral orbitofrontal cortex and sensory signals to be represented in intracalcarine sulcus. Together, our results indicate that predictive information is integrated into subjective confidence in rIFG, and reveal an occipital-frontal network that constructs confidence from top-down and bottom-up signals. This interpretation was further supported by exploratory findings that the white matter density of right orbitofrontal cortex negatively predicted its respective contribution to the construction of confidence. Our findings advance our understanding of the neural basis of subjective perceptual processes by revealing an occipitofrontal functional network that integrates prior beliefs into the construction of confidence.

  7. Expression profiles of miRNAs and involvement of miR-100 and miR-34 in regulation of cell cycle arrest in Artemia.

    PubMed

    Zhao, Ling-Ling; Jin, Feng; Ye, Xiang; Zhu, Lin; Yang, Jin-Shu; Yang, Wei-Jun

    2015-09-01

    Regulation of the cell cycle is complex but critical for proper development, reproduction and stress resistance. To survive unfavourable environmental conditions, the crustacean Artemia produces diapause embryos whose metabolism is maintained at extremely low levels. In the present study, the expression profiles of miRNAs during Artemia diapause entry and termination were characterized using high-throughput sequencing. A total of 13 unclassified miRNAs and 370 miRNAs belonging to 87 families were identified; among them, 107 were differentially expressed during diapause entry and termination. We focused on the roles of two of these miRNAs, miR-100 and miR-34, in regulating cell cycle progression; during the various stages of diapause entry, these miRNAs displayed opposing patterns of expression. A functional analysis revealed that miR-100 and miR-34 regulate the cell cycle during diapause entry by targeting polo-like kinase 1 (PLK1), leading to activation of the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase-ribosomal S6 kinase 2 (MEK-ERK-RSK2) pathway and cyclin K, leading to suppression of RNA polymerase II (RNAP II) activity respectively. The findings presented in the present study provide insights into the functions of miR-100 and miR-34 and suggest that the expression profiles of miRNAs in Artemia can be used to characterize their functions in cell cycle regulation.

  8. 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

  9. miRBase: the microRNA sequence database.

    PubMed

    Griffiths-Jones, Sam

    2006-01-01

    The miRBase Sequence database is the primary repository for published microRNA (miRNA) sequence and annotation data. miRBase provides a user-friendly web interface for miRNA data, allowing the user to search using key words or sequences, trace links to the primary literature referencing the miRNA discoveries, analyze genomic coordinates and context, and mine relationships between miRNA sequences. miRBase also provides a confidential gene-naming service, assigning official miRNA names to novel genes before their publication. The methods outlined in this chapter describe these functions. miRBase is freely available to all at http://microrna.sanger.ac.uk/.

  10. Transcriptional regulation of mammalian miRNA genes

    PubMed Central

    Schanen, Brian C.; Li, Xiaoman

    2010-01-01

    MicroRNAs (miRNAs) are members of a growing family of non-coding transcripts, 21-23 nucleotides long, which regulate a diverse collection of biological processes and various diseases by RNA-mediated gene-silencing mechanisms. While currently many studies focus on defining the regulatory functions of miRNAs, few are directed towards how miRNA genes are themselves transcriptionally regulated. Recent studies of miRNA transcription have elucidated RNA polymerase II as the major polymerase of miRNAs, however, little is known of the structural features of miRNA promoters, especially those of mammalian miRNAs. Here, we review the current literature regarding features conserved among miRNA promoters useful for their detection and the current novel methodologies available to enable researchers to advance our understanding of the transcriptional regulation of miRNA genes. PMID:20977933

  11. miRandb: a resource of online services for miRNA research.

    PubMed

    Aghaee-Bakhtiari, Seyed Hamid; Arefian, Ehsan; Lau, Pierre

    2017-01-03

    Recent discovery of thousands of small and large noncoding RNAs, in parallel to technical improvements enabling scientists to study the transcriptome in much higher depth, has resulted in massive data generation. This burst of information prompts the development of easily accessible resources for storage, retrieval and analysis of raw and processed data, and hundreds of Web-based tools dedicated to these tasks have been made available. However, the increasing number and diversity of bioinformatics tools, each covering a specific and specialized area, as well as their redundancies, represent potential sources of complication for end users. To overcome these issues, we are introducing an easy-to-follow classification of microRNA (miRNA)-related bioinformatics tools for biologists interested in studying this important class of small noncoding RNAs. We also developed our miRNA database miRNA algorithmic network database (miRandb) that is a meta-database, which presents a survey of > 180 Web-based miRNA databases. These include miRNA sequence, discovery, target prediction, target validation, expression and regulation, functions and their roles in diseases, interactions in cellular pathways and networks and deep sequencing. miRandb recapitulates the diverse possibilities and facilitates that access to the different categories of miRNA resources. Researchers can easily select the category of miRNA information and desired organism, in result eligible databases with their features are presented. This database introducing an easy-to-follow classification of available resources that can facilitate selection of appropriate resources for miRNA-related bioinformatics tools. Finally, we described current shortages and future necessities that assist researchers to use these tools easily. Our database is accessible at http://mirandb.ir.

  12. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  13. 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

  14. 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.

  15. 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

  16. miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer.

    PubMed

    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.

  17. RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection

    PubMed Central

    Van Aelst, L. N. L.; Summer, G.; Li, S.; Gupta, S. K.; Heggermont, W.; De Vusser, K.; Carai, P.; Naesens, M.; Van Cleemput, J.; Van de Werf, F.; Vanhaecke, J.; Thum, T.; Waer, M.; Papageorgiou, A.‐P.; Schroen, B.

    2015-01-01

    Acute cellular rejection (ACR) is the adverse response of the recipient's immune system against the allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine allogeneic grafts, we profiled implicated microRNAs (miRs) and mRNAs. MiR profiling showed that miR‐21, ‐142‐3p, ‐142‐5p, ‐146a, ‐146b, ‐155, ‐222, ‐223, and ‐494 increased during ACR in humans and mice, whereas miR‐149‐5p decreased. mRNA profiling revealed 70 common differentially regulated transcripts, all involved in immune signaling and immune‐related diseases. Interestingly, 33 of 70 transcripts function downstream of IL‐6 and its transcription factor spleen focus forming virus proviral integration oncogene (SPI1), an established target of miR‐155, the most upregulated miR in human EMBs manifesting rejection. In a mouse model of cardiac transplantation, miR‐155 absence and pharmacological inhibition attenuated ACR, demonstrating the causal involvement and therapeutic potential of miRs. Finally, we corroborated our miR signature in acute cellular renal allograft rejection, suggesting a nonorgan specific signature of acute rejection. We concluded that miR and mRNA profiling in human and murine ACR revealed the shared significant dysregulation of immune genes. Inflammatory miRs, for example miR‐155, and transcripts, in particular those related to the IL‐6 pathway, are promising therapeutic targets to prevent acute allograft rejection. PMID:26249758

  18. miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers.

    PubMed

    Fkih M'hamed, Insaf; Privat, Maud; Trimeche, Mounir; Penault-Llorca, Frédérique; Bignon, Yves-Jean; Kenani, Abderraouf

    2017-01-18

    MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that can post-transcriptionally regulate gene expression and have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. About 1000 genes in humans encode miRNAs, which account for approximately 3% of the human genome, and up to 30% of human protein coding genes may be regulated by miRNAs. The objective of this article is to evaluate the expression profile of four miRNAs previously implicated in triple negative breast cancer: miR-10b, miR-26a, miR-146a and miR-153, and to determine their possible interaction in triple negative and non triple negative breast cancer based on clinical outcome and the expression of BRCA1. 24 triple-negative and 13 non triple negative breast cancer cases, were studied by q-RT-PCR and immunohistochemistry to determine the expression of the four studied miRNAs and the BRCA1 protein, respectively. We observed that the BRCA1 protein was absent in 62.5% of the triple negative cases. Besides, the miR-146a and miR-26a were over expressed in triple negative breast cancer. These two miRNAs, miR-10b and miR-153 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma. All the analyzed microRNAs were not associated with the expression of BRCA1 in our conditions. Our work provides evidence that miR-146a, miR-26a, miR-10b and miR-153 could be defined as biomarkers in triple negative breast cancer to predict lymph node metastases (LNM).

  19. 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

  20. Ten-year experience of retrievable inferior vena cava filters in a tertiary referral center

    PubMed Central

    Tse, George; Cleveland, Trevor; Goode, Stephen

    2017-01-01

    PURPOSE A significant proportion of patients undergoing surgery have an increased incidence of acute pulmonary embolus (PE). We analyzed all patients who had a retrievable inferior vena cava (IVC) filter placed preoperatively for PE prophylaxis and investigated the long-term outcomes of the patients who did not have their filter removed. METHODS Patients who underwent retrievable IVC filter insertion and attempted removal were identified from the radiology information systems database in a large tertiary referral university teaching hospital. Results of all clinical investigations (including computed tomography, magnetic resonance imaging, ultrasonography, and plain radiography) while the IVC filters were in situ were reviewed. RESULTS In total, 393 retrievable IVC filters were inserted, 254 with the indication of preoperative thromboembolic prophylaxis. Recurrent PE was reported in five patients (1.9%) despite the IVC filter. Of the 254 retrievable filters inserted prior to surgery, an attempt at retrieval was made in 168 filters (66.1%). Successful retrieval at the first attempt occurred in 143 cases (85.1%), while 25 cases failed or were aborted (14.9%). No attempt at retrieval was made in 86 (33.9%) patients and a significant proportion of these patients had undergone cancer surgery (P < 0.0107). In those patients where there was no attempt at retrieval, there was an association between cancer surgery and a shorter absolute survival time (P < 0.0001). CONCLUSION The majority of attempted filter retrievals were successful, and a proportion of nonretrieved IVC filters are accounted for in patients who underwent cancer surgery and ultimately died with the filter in situ. A departmental protocol is recommended to ensure the filter is removed where appropriate and possible. PMID:28093377

  1. 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

  2. The regulation roles of miR-125b, miR-221 and miR-27b in porcine Salmonella infection signalling pathway.

    PubMed

    Yao, Min; Gao, Weihua; Yang, Jun; Liang, Xiongyan; Luo, Jingbo; Huang, Tinghua

    2016-08-01

    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.

  3. Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion

    PubMed Central

    Shin, Yoon Mi; Yun, Jieun; Lee, Ok-Jun; Lim, Sung-Nam; An, Jin Young; Lee, Ki Hyeong; Lee, Ki Man; Choe, Kang Hyeon

    2014-01-01

    Purpose The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). Materials and Methods Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA). Results The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. Conclusion The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE. PMID:24851110

  4. Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs

    PubMed Central

    Ranjha, Raju; Meena, Naresh Kumar; Singh, Abhiraman; Ahuja, Vineet; Paul, Jaishree

    2017-01-01

    Background and aim MicroRNAs are small non-coding RNAs that play an important role in regulating the gene expression of their target genes. SNP miR-196a-2 rs11614913 and miR-499 rs3746444 are reported to have association with the risk and prognosis of multiple-types of inflammatory diseases including IBD. This study was conducted to show if any association of SNP miR-196a-2rs11614913 and miR-499 rs3746444 exists with ulcerative colitis (UC) patients of north Indian population and how these polymorphisms modulate the expression profile of the respective miRNAs. Methods A total of 638 participants including 197 UC patients and 441 controls were included in this study. Polymorphisms were genotyped by PCR-RFLP and the miRNA expression was measured using qRT-PCR. Genotypes and allele frequencies were calculated using SPSS 16 software. Results MiR-196a-2 rs11614913 (C>T) and miR-499 rs3746444 (T>C) were found to be associated with UC. TT genotype of miR-196a-2 rs11614913 (p = 0.03) was negatively associated with UC whereas the heterozygous TC genotype of miR-499 rs3746444 (p = 0.003) was showing positive association with UC. Patients having a combination of both SNPs, developed disease at older age and they suffered from severe disease extent. Genotype that showed association with the disease also showed correlation with the changes in miRNA expression. Conclusion In this study we found miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression. PMID:28301487

  5. Involvement of miRNAs in equine follicle development.

    PubMed

    Schauer, S N; Sontakke, S D; Watson, E D; Esteves, C L; Donadeu, F X

    2013-09-01

    Previous evidence from in vitro studies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to determine changes in the levels of these miRNAs in relation to follicle selection, maturation, and ovulation in the monovular equine ovary. In Experiment 1, follicular fluid was aspirated during ovulatory cycles from the dominant (DO) and largest subordinate (S) follicles of an ovulatory wave and the dominant (DA) follicle of a mid-cycle anovulatory wave (n=6 mares). Follicular fluid levels of progesterone and estradiol were lower (P<0.01) in S follicles than in DO follicles, whereas mean levels of IGF1 were lower (P<0.01) in S and DA follicles than in DO follicles. Relative to DO and DA follicles, S follicles had higher (P≤0.01) follicular fluid levels of miR-145 and miR-378. In Experiment 2, follicular fluid and granulosa cells were aspirated from dominant follicles before (DO) and 24 h after (L) administration of an ovulatory dose of hCG (n=5 mares/group). Relative to DO follicles, L follicles had higher follicular fluid levels of progesterone (P=0.05) and lower granulosa cell levels of CYP19A1 and LHCGR (P<0.005). Levels of miR-21, miR-132, miR-212, and miR-224 were increased (P<0.05) in L follicles; this was associated with reduced expression of the putative miRNA targets, PTEN, RASA1, and SMAD4. These novel results may indicate a physiological involvement of miR-21, miR-145, miR-224, miR-378, miR-132, and miR-212 in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular ovary.

  6. 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

  7. Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines

    PubMed Central

    Mundalil Vasu, Mahesh; Anitha, Ayyappan; Takahashi, Taro; Thanseem, Ismail; Iwata, Keiko; Asakawa, Tetsuya; Suzuki, Katsuaki

    2016-01-01

    Evidence suggests neuroprotective effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on the developed neurons in the adult brain. In contrast, the drug may be deleterious to immature or undifferentiated neural cells, although the mechanism is unclear. Recent investigations have suggested that microRNAs (miRNA) may be critical for effectiveness of psychotropic drugs including SSRI. We investigated whether fluoxetine could modulate expressions of neurologically relevant miRNAs in two neuroblastoma SK-N-SH and SH-SY5Y cell lines. Initial screening results revealed that three (miR-489, miR-572 and miR-663a) and four (miR-320a, miR-489, miR-572 and miR-663a) miRNAs were up-regulated in SK-N-SH cells and SH-SY5Y cells, respectively, after 24 hours treatment of fluoxetine (1–25 μM). Cell viability was reduced according to the dose of fluoxetine. The upregulation of miR-572 and miR-663a was consistent in both the SH-SY5Y and SK-N-SH cells, confirmed by a larger scale culture condition. Our data is the first in vitro evidence that fluoxetine could increase the expression of miRNAs in undifferentiated neural cells, and that putative target genes of those miRNAs have been shown to be involved in fundamental neurodevelopmental processes. PMID:27716787

  8. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development.

    PubMed

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-02-14

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.

  9. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    PubMed Central

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-01-01

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches. PMID:28216603

  10. Identification of miR414 and expression analysis of conserved miRNAs from Stevia rebaudiana.

    PubMed

    Guleria, Praveen; Yadav, Sudesh Kumar

    2011-12-01

    MicroRNAs (miRNAs) usually contain 19-24 nucleotides and have been identified as important eukaryotic gene regulators. Applications of various computational approaches have simplified the task by predicting miRNAs from available sequence data sources. In this study, we identified a conserved miR414 from a computational analysis of EST sequence data available from Stevia rebaudiana. In addition, we also identified six conserved miRNAs namely miR169, miR319, miR414, miR164, miR167 and miR398 using stem-loop RT-PCR analysis. Hence, miR414 was commonly identified using both methods. The expression analysis of these miRNAs documented their roles in growth and development of Stevia. Furthermore, the detected miRNAs were found to target genes involved in plant growth, development, metabolism and signal transduction. This is the first study reporting these conserved miRNAs and their expression in Stevia.

  11. Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial

    PubMed Central

    Toffolo, Antonella; Zucchetta, Pietro; Dall'Amico, Roberto; Gobber, Daniela; Calderan, Alessandro; Maschio, Francesca; Pavanello, Luigi; Molinari, Pier Paolo; Scorrano, Dante; Zanchetta, Sergio; Cassar, Walburga; Brisotto, Paolo; Corsini, Andrea; Sartori, Stefano; Dalt, Liviana Da; Murer, Luisa; Zacchello, Graziella

    2007-01-01

    Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. Design Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. Setting 28 paediatric units in north east Italy. Participants 502 children aged 1 month to <7 years with clinical pyelonephritis. Intervention Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37°C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. Results Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk −4%, 95% confidence interval −11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (−0.9 to 6.0); white cell count 9.8×109/l (SD 3.5) v 9.5×109/l (SD 3.1), mean difference 0.3 (−0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference −0.05% (−1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. Trial registration Clinical Trials

  12. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  13. Bronchitis - acute

    MedlinePlus

    ... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  14. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

  15. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    NASA Astrophysics Data System (ADS)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    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.

  16. Analysis of weekend effect on 30-day mortality among patients with acute myocardial infarction

    PubMed Central

    Noad, Rebecca; Stevenson, Michael; Herity, Niall A

    2017-01-01

    Objectives Several publications have demonstrated increased 30-day mortality in patients admitted on Saturdays or Sundays compared with weekdays. We sought to determine whether this was true for two different cohorts of patients admitted with acute myocardial infarction (MI). Methods and results Thirty-day mortality data were obtained for 3757 patients who had been admitted to the Belfast Health and Social Care Trust with acute MI between 2009 and 2015. They were subdivided into those presenting with ST elevation MI (n=2240) and non-ST elevation MI (n= 1517). We observed no excess 30-day mortality in those admitted over weekends. Conclusion Excess mortality in patients admitted at weekends is not a universal finding. This may mean that that there are patient subgroups with proportionately greater weekend hazard and points to the need for more detailed understanding of the weekend effect.

  17. Inferior vena cava filter retrievals, standard and novel techniques

    PubMed Central

    Walker, T. Gregory

    2016-01-01

    The placement of an inferior vena cava (IVC) filter is a well-established management strategy for patients with venous thromboembolism (VTE) disease in whom anticoagulant therapy is either contraindicated or has failed. IVC filters may also be placed for VTE prophylaxis in certain circumstances. There has been a tremendous growth in placement of retrievable IVC filters in the past decade yet the majority of the devices are not removed. Unretrieved IVC filters have several well-known complications that increase in frequency as the filter dwell time increases. These complications include caval wall penetration, filter fracture or migration, caval thrombosis and an increased risk for lower extremity deep vein thrombosis (DVT). Difficulty is sometimes encountered when attempting to retrieve indwelling filters, mainly because of either abnormal filter positioning or endothelization of filter components that are in contact with the IVC wall, thereby causing the filter to become embedded. The length of time that a filter remains indwelling also impacts the retrieval rate, as increased dwell times are associated with more difficult retrievals. Several techniques for difficult retrievals have been described in the medical literature. These techniques range from modifications of standard retrieval techniques to much more complex interventions. Complications related to complex retrievals are more common than those associated with standard retrieval techniques. The risks of complex filter retrievals should be compared with those of life-long anticoagulation associated with an unretrieved filter, and should be individualized. This article summarizes current techniques for IVC filter retrieval from a clinical point of view, with an emphasis on advanced retrieval techniques. PMID:28123984

  18. 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.

  19. 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.

  20. Multiple components of ipsilaterally evoked inhibition in the inferior colliculus.

    PubMed

    Klug, A; Bauer, E E; Pollak, G D

    1999-08-01

    The central nucleus of the inferior colliculus (ICc) receives a large number of convergent inputs that are both excitatory and inhibitory. Although excitatory inputs typically are evoked by stimulation of the contralateral ear, inhibitory inputs can be recruited by either ear. Here we evaluate ipsilaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. The principal question we addressed concerns the degree to which ipsilateral inhibition at the ICc suppresses contralaterally evoked discharges and thus creates the excitatory-inhibitory (EI) properties of ICc neurons. To study ipsilaterally evoked inhibition, we iontophoretically applied excitatory neurotransmitters and visualized the ipsilateral inhibition as a gap in the carpet of background activity evoked by the transmitters. Ipsilateral inhibition was seen in 86% of ICc cells. The inhibition in most cells had both glycinergic and GABAergic components that could be blocked by the iontophoretic application of bicuculline and strychnine. In 80% of the cells that were inhibited, the ipsilateral inhibition and contralateral excitation were temporally coincident. In many of these cells, the ipsilateral inhibition suppressed contralateral discharges and thus generated the cell's EI property in the ICc. In other cells, the ipsilateral inhibition was coincident with the initial portion of the excitation, but the inhibition was only 2-4 ms in duration and suppressed only the first few contralaterally evoked discharges. The suppression was so slight that it often could not be detected as a decrease in the spike count generated by increasing ipsilateral intensities. Twenty percent of the cells that expressed inhibition, however, had inhibitory latencies that were longer than the excitatory latencies. In these neurons, the inhibition arrived too late to suppress most or any of the discharges. Finally, in the majority of cells, the ipsilateral inhibition persisted for tens of milliseconds beyond

  1. 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).

  2. MiR-145-5p regulates hypoxia-induced inflammatory response and apoptosis in cardiomyocytes by targeting CD40.

    PubMed

    Yuan, Ming; Zhang, Liwei; You, Fei; Zhou, Jingyu; Ma, Yongjiang; Yang, Feifei; Tao, Ling

    2017-03-09

    An increasing body of evidence indicates that inflammation and apoptosis are involved in the development of acute myocardial infarction (AMI). In this study, we sought to investigate the specific role and the underlying regulatory mechanism of miR-145-5p in myocardial ischemic injury. H9c2 cardiac cells were exposed to hypoxia to establish a model of myocardial hypoxic/ischemic injury. We found that miR-145-5p was notably down-regulated, while CD40 expression was highly elevated in H9c2 cells following exposure to acute hypoxia. Additionally, hypoxia markedly enhanced the inflammatory response, as reflected by an increase in the secretion of the cytokines IL-1β, TNF-α, and IL-6, whereas the introduction of miR-145-5p effectively suppressed inflammatory factor production triggered by hypoxia. Furthermore, we observed hypoxia stimulation significantly augmented apoptosis accompanied by a decrease in the expression of Bcl-2 and an increase in the expression of Bax, Caspase-3, and Caspase-9. However, augmentation of miR-145-5p led to a dramatic prevention of hypoxia-induced apoptosis. Importantly, we identified CD40 as a direct target of miR-145-5p. Interestingly, the depletion of CD40 with small interfering RNAs (siRNAs) apparently repressed the production of inflammatory cytokines and apoptosis in the setting of acute hypoxic treated. Taken together, these data demonstrated that miR-145-5p may function as a cardiac-protective molecule in myocardial ischemic injury by ameliorating inflammation and apoptosis via negative regulation of CD40. The study gives evidence that miR-145-5p provides an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response and apoptosis.

  3. Regulation of miR-34 Family in Neuronal Development.

    PubMed

    Jauhari, Abhishek; Singh, Tanisha; Singh, Parul; Parmar, Devendra; Yadav, Sanjay

    2017-01-13

    Differentiation of neural stem cells (NSC's) to mature and functional neurons requires coordinated expression of mRNA, microRNAs (miRNAs) and regulatory proteins. Our earlier unbiased miRNA profiling studies have identified miR-200, miR-34 and miR-221/222 as maximally up-regulated miRNA families in differentiating PC12 cells and demonstrated the capability of miR-200 family in inducing neuronal differentiation (J. Neurochem, 2015, 133, 640-652). In present study, we have investigated role of miR-34 family in neuronal differentiation and identified P53 as mediator of nerve growth factor (NGF) induced miR-34a expression in differentiating PC12 cells. Our studies have shown that NGF induced miR-34a, arrests proliferating PC12 cells to G1 phase, which is pre-requisite for neuronal differentiation. Our studies have also shown that increased expression of miR-34a controls the P53 level in differentiated PC12 cells in feedback inhibition manner, which probably prevents differentiated cells from P53 induced apoptosis. Expression profiling of miR-34 family in different neuronal, non-neuronal and developing cells have identified differentiated and aged brain cells as richest source of miR-34, which also indicates that higher expression of miR-34 family helps in maintaining the mature neurons in non-proliferative stage. In conclusion, our studies have shown that miR-34 is brain enriched miRNA family, which up-regulates with neuronal maturation and brain ageing and co-operative regulation of P53 and miR-34a helps in neuronal differentiation by arresting cells in G1 phase.

  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).

  5. TREM-1-accentuated lung injury via miR-155 is inhibited by LP17 nanomedicine

    PubMed Central

    Yuan, Zhihong; Syed, Mansoor; Panchal, Dipti; Joo, Myungsoo; Bedi, Chetna; Lim, Sokbee; Onyuksel, Hayat; Rubinstein, Israel; Colonna, Marco

    2015-01-01

    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

  6. miEAA: microRNA enrichment analysis and annotation

    PubMed Central

    Backes, Christina; Khaleeq, Qurratulain T.; Meese, Eckart; Keller, Andreas

    2016-01-01

    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

  7. 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.

  8. miRNA-encoded peptides (miPEPs): A new tool to analyze the roles of miRNAs in plant biology

    PubMed Central

    Couzigou, Jean-Malo; Lauressergues, Dominique; Bécard, Guillaume; Combier, Jean-Philippe

    2015-01-01

    MicroRNAs (miRNAs) are short RNA molecules negatively regulating the expression of many important genes in plants and animals. We have recently shown that plant primary transcripts of miRNAs encode peptides (miPEPs) able to increase specifically the transcription of their associated miRNA.1 We discuss here the possibility of using miPEPs as a new tool for functional analysis of single members of miRNA families in plants, including in non-model plants, that could avoid transgenic transformation and minimize artifactual interpretation. We also raise several fundamental and crucial questions that need to be address for a deeper understanding of the cellular and molecular mechanisms underlining the regulatory activity of miPEPs. PMID:26400469

  9. miRNA-encoded peptides (miPEPs): A new tool to analyze the roles of miRNAs in plant biology.

    PubMed

    Couzigou, Jean-Malo; Lauressergues, Dominique; Bécard, Guillaume; Combier, Jean-Philippe

    2015-01-01

    MicroRNAs (miRNAs) are short RNA molecules negatively regulating the expression of many important genes in plants and animals. We have recently shown that plant primary transcripts of miRNAs encode peptides (miPEPs) able to increase specifically the transcription of their associated miRNA.(1) We discuss here the possibility of using miPEPs as a new tool for functional analysis of single members of miRNA families in plants, including in non-model plants, that could avoid transgenic transformation and minimize artifactual interpretation. We also raise several fundamental and crucial questions that need to be address for a deeper understanding of the cellular and molecular mechanisms underlining the regulatory activity of miPEPs.

  10. Retinoic acid influences the development of the inferior olivary nucleus in the rodent.

    PubMed

    Yamamoto, Miyuki; Fujinuma, Masahiro; Hirano, Shinji; Hayakawa, Yoshika; Clagett-Dame, Margaret; Zhang, Jinghua; McCaffery, Peter

    2005-04-15

    All-trans retinoic acid (atRA) is an endogenous morphogen that regulates gene transcription. Maternal exposure to atRA results in severe developmental abnormalities by disrupting normal patterns of atRA distribution. Previously, we have shown that the pontine nucleus, which originates from the rhombic lip, is severely atrophied in the mouse on exposure to atRA at gestational days 9 and 10. In this study, we show that this same period of atRA exposure has the contrary effect on the inferior olive and this rhombic lip derivative is expanded in volume and probably contains an increased number of cells. The posterior region of the inferior olive maintains a relatively normal shape but is significantly expanded in size. In contrast, the organization of the anterior inferior olive is severely disrupted. Because endogenous atRA levels are known to be higher in the region of the posterior inferior olive at the time of birth of inferior olivary neurons, these results suggest that endogenous atRA may promote the generation, or select the fate, of posterior neurons of the inferior olive. In support of this concept, a reduction in atRA resulting from vitamin A deficiency results in loss of cells of the posterior inferior olive.

  11. Study of the inferior colliculus in patients with schizophrenia by magnetic resonance spectroscopy.

    PubMed

    Martinez-Granados, B; Martinez-Bisbal, M C; Sanjuan, J; Aguilar, E J; Marti-Bonmati, L; Molla, E; Celda, B

    2014-07-01

    INTRODUCTION. Previous studies have suggested morphometric and functional abnormalities in the inferior colliculus in patients with schizophrenia. Auditory hallucinations are one of the central symptoms in schizophrenia. In this complex and multidimensional event both attention and emotion are thought to play a key role. AIM. To study metabolic changes in the inferior colliculus, a nucleus integrated in the auditory pathway, in patients with schizophrenia and the possible relationship with auditory hallucinations. SUBJECTS AND METHODS. Magnetic resonance spectroscopic imaging studies were performed in 30 right-handed patients with chronic schizophrenia (19 of them with auditory hallucinations) and 28 controls. A magnetic resonance spectroscopic imaging 2D slice was acquired and the voxels representative of both inferior colliculi were selected. N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) peak areas were measured. RESULTS. The patients with schizophrenia showed a NAA/Cr significant reduction in the right inferior colliculus compared to the control subjects. The metabolic data in the right inferior colliculus were correlated with emotional auditory hallucinations items. CONCLUSIONS. The contribution of the inferior colliculus on neural underpinnings of auditory hallucinations is particularly relevant for the right inferior colliculus and is centered on attention-emotional component of this symptom.

  12. Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

    PubMed Central

    Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

    2014-01-01

    Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

  13. MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

    PubMed Central

    Budak, Ferah; Bal, S. Haldun; Tezcan, Gulcin; Guvenc, Furkan; Akalin, E. Halis; Goral, Guher; Deniz, Gunnur

    2016-01-01

    Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis. PMID:27824867

  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.

  15. The human rs1050286 polymorphism alters LOX-1 expression through modifying miR-24 binding.

    PubMed

    Morini, Elena; Rizzacasa, Barbara; Pucci, Sabina; Polidoro, Chiara; Ferrè, Fabrizio; Caporossi, Daniela; Helmer Citterich, Manuela; Novelli, Giuseppe; Amati, Francesca

    2016-01-01

    The up-regulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX-1 overexpression is crucial. Predictive analysis showed a putative hsa-miR-24 binding site in the 3'UTR of OLR1, 'naturally' mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR-24 targets OLR1 3'UTR-G, but not 3'UTR-A (P < 0.0005). The functional relevance of miR-24 in regulating the expression of OLR1 was established by overexpressing miR-24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down-regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR-24 binding affinity to the 3'UTR of OLR1, causing a more efficient post-transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk.

  16. Comparative mRNA and MicroRNA Profiling during Acute Myocardial Infarction Induced by Coronary Occlusion and Ablation Radio-Frequency Currents

    PubMed Central

    Santana, Eduardo T.; Feliciano, Regiane dos Santos; Serra, Andrey J.; Brigidio, Eduardo; Antonio, Ednei L.; Tucci, Paulo J. F.; Nathanson, Lubov; Morris, Mariana; Silva, José A.

    2016-01-01

    The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality. In addition, cardiac structural, and functional changes aroused by AB-RF were similar to those seen in animals with MI induced by coronary artery ligation. Herein, we compared mRNA expression of genes that govern post-MI milieu in occlusion and ablation models. We analyzed 48 mRNAs expressions of nine different signal transduction pathways (cell survival and metabolism signs, matrix extracellular, cell cycle, oxidative stress, apoptosis, calcium signaling, hypertrophy markers, angiogenesis, and inflammation) in rat left ventricle 1 week after MI generated by both coronary occlusion and AB-RF. Furthermore, high-throughput miRNA analysis was also assessed in both MI procedures. Interestingly, mRNA expression levels and miRNA expressions showed strong similarities between both models after MI, with few specificities in each model, activating similar signal transduction pathways. To our knowledge, this is the first comparison of genomic alterations of mRNA and miRNA contents after two different MI procedures and identifies key signaling regulators modulating the pathophysiology of these two models that might culminate in heart failure. Furthermore, these analyses may contribute with the current knowledge concerning transcriptional and post-transcriptional changes of AB-RF protocol, arising as an alternative and effective MI method that reproduces most changes seem in coronary occlusion. PMID:27932994

  17. Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia.

    PubMed

    Wang, Zhengyan; Hong, Ze; Gao, Feng; Feng, Weijing

    2013-11-01

    A genome-wide serum miRNA expression analysis previously showed the upregulation of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with healthy controls. The aim of this study was to investigate the expression patterns and the prognostic relevance of miR-375 in pediatric AML. Expression levels of miR-375 in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. Expression levels of miR-375 in the bone marrow of pediatric AML patients were significantly higher than those in normal controls (P < 0.001). Then, miR-375 upregulation occurred more frequently in French-American-British classification subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the expression levels of miR-375 in pediatric AML patients with unfavorable karyotypes were dramatically higher than those in intermediate and favorable groups (P = 0.002). Moreover, high miR-375 expression was significantly associated with shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001) in pediatric AML patients. Multivariate analysis further identified miR-375 expression and cytogenetics risk as independent prognostic factors for both relapse-free survival and overall survival. In particular, the prognostic relevance of miR-375 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our findings suggest for the first time that the upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric AML. Since its correlation with poor relapse-free survival and overall survival, miR-375 may be a novel biomarker to improve the management of pediatric AML patients.

  18. miR-155: A Novel Target in Allergic Asthma

    PubMed Central

    Zhou, Hong; Li, Junyao; Gao, Peng; Wang, Qi; Zhang, Jie

    2016-01-01

    MicroRNAs (miRNAs), a class of small non-coding RNAs of 18–24 nucleotides in length, function to posttranscriptionally regulate protein expression. miR-155 was one of the first identified and, to date, the most studied miRNA, and has been linked to various cellular processes such as modulation of immune responses and oncogenesis. Previous studies have identified miR-155 as a crucial positive regulator of Th1 immune response in autoimmune diseases, but as a suppressor of Th2 immunity in allergic disorders. However, recent studies have found new evidence that miR-155 plays an indispensible role in allergic asthma. This review summarizes the recent findings with respect to miR-155 in immune responses and the underlying mechanisms responsible for miR-155-related allergic diseases, as well as the similarities between miR-155 and glucocorticoids in immunity. PMID:27783037

  19. Fitness and structure landscapes for pre-miRNA processing

    NASA Astrophysics Data System (ADS)

    Bundschuh, Ralf; de Meaux, Juliette; Lassig, Michael

    2011-03-01

    The processing from pre-miRNA to mature miRNA in plants involves a mechanism, which depends on an extended stem in the secondary structure of the pre-miRNA. Here, we show how natural selection acts on this secondary structure to produce evolutionary conservation of the processing mechanism together with modularity of the pre-miRNA molecules, making this molecular function independent of others. Our main results are: 1. Selection on miRNA processing can be described by a fitness landscape which depends directly on the secondary structure of the pre-miRNA. 2. This fitness landscape predicts the divergence of the phenotype between orthologous pre-miRNA molecules from different species. 3. Actual pre-miRNA structures are modular: their phenotype is significantly less affected by deleterious mutations in the remainder of the molecule than for random RNA molecules.

  20. RNA Binding Proteins in the miRNA Pathway.

    PubMed

    Connerty, Patrick; Ahadi, Alireza; Hutvagner, Gyorgy

    2015-12-26

    microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.

  1. 21. Photocopy of drawing (from Sault Ste. Marie, MI city ...

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

    21. Photocopy of drawing (from Sault Ste. Marie, MI city archives) showing ROADWAY ACROSS SECTION DETAILS - Spruce Street Bridge, East Spruce Street, 500 Block, spanning Power Canal, Sault Ste. Marie, Chippewa County, MI

  2. miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes

    SciTech Connect

    McKenna, Declan J.; Patel, Daksha; McCance, Dennis J.

    2014-01-05

    A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR-24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16 (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during proliferation and differentiation of HFKs. We show that the induction of both miR-24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as miR-205 expression is dependent on pRb expression. Finally, we provide evidence that miR-24 effects in the cell may be due to targeting of cyclin dependent kinase inhibitor p27. In summary, these results indicate that expression of both miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one mechanism by which HPV onco-proteins can disrupt the balance between proliferation and differentiation in keratinocytes. - Highlights: • miR-24 and miR-205 are induced during keratinocyte differentiation. • This induction is lost in keratinocytes expressing HPV onco-proteins E6 and E7. • miR-205 is dependent upon pRb expression. • miR-24 targets p27 in cycling keratinocytes.

  3. Overexpression of miR-484 and miR-744 in Vero cells alters Dengue virus replication

    PubMed Central

    Castrillón-Betancur, Juan Camilo; Urcuqui-Inchima, Silvio

    2017-01-01

    BACKGROUND Dengue is considered one of the world’s most important mosquito-borne diseases. MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that play an important role in the regulation of gene expression in eukaryotes. Although miRNAs possess antiviral activity against many mammalian-infecting viruses, their involvement in Dengue virus (DENV) replication remains poorly understood. OBJECTIVE To determine the role of miR-484 and miR-744 in DENV infection and to examine whether DENV infection alters the expression of both miRNAs. METHODS We used bioinformatics tools to explore the relationship between DENV and cellular miRNAs. We then overexpressed miR-484 or miR-744 in Vero cells to examine their role in DENV replication using flow cytometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and western blotting. FINDINGS We found several cellular miRNAs that target a conserved region within the 3′ untranslated region (3′ UTR) of the genome of the four DENV serotypes and found that overexpression of miR-484 or miR-744 inhibits infection by DENV-1 to DENV-4. Furthermore, we observed that DENV RNA might be involved in the downregulation of endogenous miR-484 and miR-744. CONCLUSION Our study identifies miR-484 and miR-744 as two possible restriction host factors against DENV infection. However, further studies are needed to directly verify whether miR-484 and miR-744 both have an anti-DENV effect in vivo. PMID:28327787

  4. miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells.

    PubMed

    Salah, Zaidoun; Arafeh, Rand; Maximov, Vadim; Galasso, Marco; Khawaled, Saleh; Abou-Sharieha, Samah; Volinia, Stefano; Jones, Kevin B; Croce, Carlo M; Aqeilan, Rami I

    2015-03-10

    Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR-27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR-27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.

  5. miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells

    PubMed Central

    Maximov, Vadim; Galasso, Marco; Khawaled, Saleh; Abou-Sharieha, Samah; Volinia, Stefano; Jones, Kevin B.; Croce, Carlo M.; Aqeilan, Rami I.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR-27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR-27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases. PMID:25749032

  6. MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation.

    PubMed

    Conti, Alfredo; Romeo, Sara G; Cama, Annamaria; La Torre, Domenico; Barresi, Valeria; Pezzino, Gaetana; Tomasello, Chiara; Cardali, Salvatore; Angileri, Filippo F; Polito, Francesca; Ferlazzo, Guido; Di Giorgio, Rosamaria; Germanò, Antonino; Aguennouz, M'hammed

    2016-10-01

    The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To investigate the regulatory mechanisms governing the malignant signature of gliomas with different grades of malignancy, we analyzed miRNA expression profiles in human grade I-IV tumor samples and primary glioma cell cultures. Multiplex real-time PCR was used to profile miRNA expression in a set of World Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary glioma cell cultures. Primary glioma cell cultures were used to evaluate the effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray showed that a set of miRNAs was consistently upregulated in all glioma samples. miR-363 was upregulated in all tumor specimens and cell lines, and its expression correlated with tumor grading. The transfection of glioma cells with the specific inhibitor of miR-363 increased the expression level of tumor suppressor growth-associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival, while inhibition of miR-363 significantly reduced glioma cell viability. Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1, matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3. Together, these data suggest that the upregulation of miR-363 may play a role in malignant glioma signature.

  7. Virus-Mediated Alterations in miRNA Factors and Degradation of Viral miRNAs by MCPIP1

    PubMed Central

    Happel, Christine; Ramalingam, Dhivya; Ziegelbauer, Joseph M.

    2016-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi’s sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation. We also provide evidence that KSHV miRNAs repress MCPIP1 expression by targeting the 3’UTR of MCPIP1. Conversely, expression of essential miRNA biogenesis components Dicer and TRBP is increased following latent KSHV infection. We propose that KSHV infection inhibits a negative regulator of miRNA biogenesis (MCPIP1) and up-regulates critical miRNA processing components to evade host mechanisms that inhibit expression of viral miRNAs. KSHV-mediated alterations in miRNA biogenesis represent a novel mechanism by which KSHV interacts with its host and a new mechanism for the regulation of viral miRNA expression. PMID:27893764

  8. The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b

    PubMed Central

    Zou, Qin; Tan, Shi; Yang, Zailin; Wang, Juan; Xian, Jingrong; Zhang, Shuaishuai; Jin, Hongjun; Yang, Liyuan; Wang, Lu; Zhang, Ling

    2016-01-01

    Mutations in the nucleophosmin 1 (NPM1) gene are the most frequent genetic alteration in acute myeloid leukemia (AML). Here, we showed that enforced expression of NPM1 mutation type A (NPM1-mA) inhibits myeloid differentiation of leukemia cells, whereas knockdown of NPM1-mA has the opposite effect. Our analyses of normal karyotype AML samples from The Cancer Genome Atlas (TCGA) dataset revealed that miR-10b is commonly overexpressed in NPM1-mutated AMLs. We also found high expression of miR-10b in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells. In addition, NPM1-mA knockdown enhanced myeloid differentiation, while induced expression of miR-10b reversed this effect. Finally, we showed that KLF4 is downregulated in NPM1-mutated AMLs. These results demonstrated that miR-10b exerts its effects by repressing the translation of KLF4 and that NPM1-mA inhibits myeloid differentiation through the miR-10b/KLF4 axis. This sheds new light on the effect of NPM1 mutations' on leukemogenesis. PMID:27669739

  9. Expression of Muscle-Specific MiRNA 206 in the Progression of Disease in a Murine SMA Model

    PubMed Central

    Valsecchi, Valeria; Boido, Marina; De Amicis, Elena; Piras, Antonio; Vercelli, Alessandro

    2015-01-01

    Spinal muscular atrophy (SMA) is a severe neuromuscular disease, the most common in infancy, and the third one among young people under 18 years. The major pathological landmark of SMA is a selective degeneration of lower motor neurons, resulting in progressive skeletal muscle denervation, atrophy, and paralysis. Recently, it has been shown that specific or general changes in the activity of ribonucleoprotein containing micro RNAs (miRNAs) play a role in the development of SMA. Additionally miRNA-206 has been shown to be required for efficient regeneration of neuromuscular synapses after acute nerve injury in an ALS mouse model. Therefore, we correlated the morphology and the architecture of the neuromuscular junctions (NMJs) of quadriceps, a muscle affected in the early stage of the disease, with the expression levels of miRNA-206 in a mouse model of intermediate SMA (SMAII), one of the most frequently used experimental model. Our results showed a decrease in the percentage of type II fibers, an increase in atrophic muscle fibers and a remarkable accumulation of neurofilament (NF) in the pre-synaptic terminal of the NMJs in the quadriceps of SMAII mice. Furthermore, molecular investigation showed a direct link between miRNA-206-HDAC4-FGFBP1, and in particular, a strong up-regulation of this pathway in the late phase of the disease. We propose that miRNA-206 is activated as survival endogenous mechanism, although not sufficient to rescue the integrity of motor neurons. We speculate that early modulation of miRNA-206 expression might delay SMA neurodegenerative pathway and that miRNA-206 could be an innovative, still relatively unexplored, therapeutic target for SMA. PMID:26030275

  10. Expression of Muscle-Specific MiRNA 206 in the Progression of Disease in a Murine SMA Model.

    PubMed

    Valsecchi, Valeria; Boido, Marina; De Amicis, Elena; Piras, Antonio; Vercelli, Alessandro

    2015-01-01

    Spinal muscular atrophy (SMA) is a severe neuromuscular disease, the most common in infancy, and the third one among young people under 18 years. The major pathological landmark of SMA is a selective degeneration of lower motor neurons, resulting in progressive skeletal muscle denervation, atrophy, and paralysis. Recently, it has been shown that specific or general changes in the activity of ribonucleoprotein containing micro RNAs (miRNAs) play a role in the development of SMA. Additionally miRNA-206 has been shown to be required for efficient regeneration of neuromuscular synapses after acute nerve injury in an ALS mouse model. Therefore, we correlated the morphology and the architecture of the neuromuscular junctions (NMJs) of quadriceps, a muscle affected in the early stage of the disease, with the expression levels of miRNA-206 in a mouse model of intermediate SMA (SMAII), one of the most frequently used experimental model. Our results showed a decrease in the percentage of type II fibers, an increase in atrophic muscle fibers and a remarkable accumulation of neurofilament (NF) in the pre-synaptic terminal of the NMJs in the quadriceps of SMAII mice. Furthermore, molecular investigation showed a direct link between miRNA-206-HDAC4-FGFBP1, and in particular, a strong up-regulation of this pathway in the late phase of the disease. We propose that miRNA-206 is activated as survival endogenous mechanism, although not sufficient to rescue the integrity of motor neurons. We speculate that early modulation of miRNA-206 expression might delay SMA neurodegenerative pathway and that miRNA-206 could be an innovative, still relatively unexplored, therapeutic target for SMA.

  11. Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes

    PubMed Central

    Saha, Banishree; Bruneau, Johanna C.; Kodys, Karen; Szabo, Gyongyi

    2015-01-01

    Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection–mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+–expressing and IL-10–secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization. PMID:25716995

  12. Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome.

    PubMed

    Wen, Jing; Huang, Ying; Li, Hongying; Zhang, Xupai; Cheng, Peng; Deng, Donghong; Peng, Zhigang; Luo, Jun; Zhao, Weihua; Lai, Yongrong; Liu, Zhenfang

    2017-02-21

    Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis with a high risk of transformation to acute myeloid leukemia (AML). miRNAs function as tumor suppressors and oncogenes in various cancers and regulate the differentiation potential of hematopoietic stem and progenitor cells (HSPCs). It has been suggested that miRNAs may play an important role in progression of MDS. We analyzed bone marrow samples collected from MDS patients according to different risk stratification indicated by the International Prognostic Scoring System (IPSS). We demonstrated that miR-196b-5p was up-regulated in intermediate II and higher groups, and in secondary AML (s-AML) patients in particular (P < 0.01) compared with healthy controls, suggesting that the higher expression levels are associated with increased risk of the development of MDS. We observed changes in proliferation and apoptosis in MDS-L cells following transfection with miR-196-5p mimics or inhibitors. After up-regulating the expression of miR-196b-5p, proliferation of MDS-L cells was up-regulated, whereas apoptosis was down-regulated (P < 0.05). In contrast, down-regulation of miR-196b-5p expression decreased cell proliferation and increased apoptosis (P < 0.05). We concluded that over-expression of miR-196b-5p may be closely associated with the risk of transformation to leukemia in MDS patients.

  13. Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction

    PubMed Central

    Damani, Samir; Bacconi, Andrea; Libiger, Ondrej; Chourasia, Aparajita H.; Serry, Rod; Gollapudi, Raghava; Goldberg, Ron; Rapeport, Kevin; Haaser, Sharon; Topol, Sarah; Knowlton, Sharen; Bethel, Kelly; Kuhn, Peter; Wood, Malcolm; Carragher, Bridget; Schork, Nicholas J.; Jiang, John; Rao, Chandra; Connelly, Mark; Fowler, Velia M.; Topol, Eric J.

    2013-01-01

    Acute myocardial infarction (MI), which involves the rupture of existing atheromatous plaque, remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease. Accordingly, a biomarker that can predict an impending MI is desperately needed. Here, we characterize circulating endothelial cells (CECs) using the first automated and clinically feasible CEC 3-channel fluorescence microscopy assay in 50 consecutive patients with ST-elevation myocardial infarction (STEMI) and 44 consecutive healthy controls. CEC counts were significantly elevated in MI cases versus controls with median numbers of 19 and 4 cells/ml respectively (p = 1.1 × 10−10). A receiver-operating characteristic (ROC) curve analysis demonstrated an area under the ROC curve of 0.95, suggesting near dichotomization of MI cases versus controls. We observed no correlation between CECs and typical markers of myocardial necrosis (ρ=0.02, CK-MB; ρ=−0.03, troponin). Morphologic analysis of the microscopy images of CECs revealed a 2.5-fold increase (P<0.0001) in cellular area and 2-fold increase (P<0.0001) in nuclear area of MI CECs versus healthy control, age-matched CECs, as well as CECs obtained from patients with preexisting peripheral vascular disease. The distribution of CEC images containing from 2 up to 10 nuclei demonstrates that MI patients are the only group to contain more than 3 nuclei/image, indicating that multi-cellular and multi-nuclear clusters are specific for acute MI. These data indicate that CECs may serve as promising biomarkers for the prediction of atherosclerotic plaque rupture events. PMID:22440735

  14. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    SciTech Connect

    Park, Jong-Kook; Henry, Jon C.; Jiang, Jinmai; Esau, Christine; Gusev, Yuriy; Lerner, Megan R.; Postier, Russell G.; Brackett, Daniel J.; Schmittgen, Thomas D.

    2011-03-25

    Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.

  15. 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.

  16. A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

    PubMed

    Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

    2011-07-01

    Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach.

  17. [Massive inferior vena cava thrombosis in a patient with autosomal dominant polycystic hepatorenal disease].

    PubMed

    Peces, R; Gil, F; Costero, O; Pobes, A

    2002-01-01

    We report a 68-year-old man with autosomal dominant polycystic kidney disease, who developed multiple venous thromboses (inferior vena cava, left renal vein and iliofemoral veins) caused by local compression of the intrahepatic inferior vena cava by hepatic cysts. To our knowledge this is the first reported case of inferior vena cava thrombosis caused by hepatic cysts compression. Doppler ultrasound, computed tomography, and magnetic resonance imaging were effective in documenting the venous thromboses and the underlying lesions non-invasively. Long-term anticoagulation was an efficient and safe treatment.

  18. Exosomes as miRNA Carriers: Formation-Function-Future.

    PubMed

    Yu, Xiaojie; Odenthal, Margarete; Fries, Jochen W U

    2016-12-02

    Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes' formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.

  19. Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening.

    PubMed

    Yang, Jin-shan; Li, Bao-jian; Lu, Hua-wei; Chen, Yu; Lu, Chuan; Zhu, Rui-xia; Liu, Si-hai; Yi, Qing-ting; Li, Jing; Song, Chun-hui

    2015-04-01

    Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.

  20. Targeting pre-miRNA by Peptide Nucleic Acids

    PubMed Central

    Avitabile, Concetta; Saviano, Michele; D'Andrea, Luca; Bianchi, Nicoletta; Fabbri, Enrica; Brognara, Eleonora; Gambari, Roberto; Romanelli, Alessandra

    2012-01-01

    PNAs conjugated to carrier peptides have been employed for the targeting of miRNA precursor, with the aim to develop molecules able to interfere in the pre-miRNA processing. The capability of the molecules to bind pre-miRNA has been tested in vitro by fluorescence assayes on Thiazole Orange labeled molecules and in vivo, in K562 cells, evaluating the amount of miRNA produced after treatment of cells with two amounts of PNAs. PMID:22699795

  1. 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.

  2. MiSIS: Michigan Student Information System.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing. Higher Education Management Services.

    The Michigan Student Information System (MiSIS) is the student flow component, of the Michigan Community College Occupational Education Evaluation System (MCCOEES), a comprehensive state-wide system for evaluating occupational education. It was developed by the Michigan community college system as a systematic and valid method of collecting…

  3. 78 FR 36631 - Michigan Disaster #MI-00039

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Michigan Disaster MI-00039 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... Application Deadline Date: 03/12/2014. ADDRESSES: Submit completed loan applications to: U.S. Small...

  4. Inputs to combination-sensitive neurons of the inferior colliculus.

    PubMed

    Wenstrup, J J; Mittmann, D H; Grose, C D

    1999-07-12

    In the mustached bat, combination-sensitive neurons display integrative responses to combinations of acoustic elements in biosonar or social vocalizations. One type of combination-sensitive neuron responds to multiple harmonics of the frequency-modulated (FM) components in the sonar pulse and echo of the bat. These neurons, termed FM-FM neurons, are sensitive to the pulse-echo delay and may encode the distance of sonar targets. FM-FM neurons are common in high-frequency regions of the central nucleus of the inferior colliculus (ICC) and may be created there. If so, they must receive low-frequency inputs in addition to the expected high-frequency inputs. We placed single deposits of a tracer at FM-FM recording sites in the ICC and then analyzed retrograde labeling in the brainstem and midbrain. We were particularly interested in labeling patterns suggestive of low-frequency input to these FM-FM neurons. In most nuclei containing labeled cells, there was a single focus of labeling in regions thought to be responsive to high-frequency sounds. More complex labeling patterns were observed in three nuclei. In the anteroventral cochlear nucleus, labeling in the anterior and marginal cell divisions occurred in regions thought to respond to low-frequency sounds. This labeling comprised 6% of total brainstem labeled cells. Labeling in the intermediate nucleus of the lateral lemniscus and the magnocellular part of the ventral nucleus of the lateral lemniscus together comprised nearly 40% of all labeled cells. In both nuclei, multiple foci of labeling occurred. These different foci may represent groups of cells tuned to different frequency bands. Thus, one or more of these three nuclei may provide low-frequency input to high-frequency-sensitive cells in the ICC, creating FM-FM responses. We also examined whether ICC neurons responsive to lower frequencies project to high-frequency-sensitive ICC regions; only 0.15% of labeling originated from these lower frequency

  5. Language outcomes after resection of dominant inferior parietal lobule gliomas.

    PubMed

    Southwell, Derek G; Riva, Marco; Jordan, Kesshi; Caverzasi, Eduardo; Li, Jing; Perry, David W; Henry, Roland G; Berger, Mitchel S

    2017-01-06

    OBJECTIVE The dominant inferior parietal lobule (IPL) contains cortical and subcortical regions essential for language. Although resection of IPL tumors could result in language deficits, little is known about the likelihood of postoperative language morbidity or the risk factors predisposing to this outcome. METHODS The authors retrospectively examined a series of patients who underwent resections of gliomas from the dominant IPL. Postoperative language outcomes