Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.

The Effect of Inhaled Nitric Oxide in Preterm Infants less than 1,250 g with Respiratory Failure / 대한주산의학회잡지

PURPOSE: Inhaled nitric oxide (iNO) therapy can decrease pulmonary vascular resistance and improve oxygenation through enhanced ventilation-perfusion matching. This study investigated therapeutic response and possible factors affecting the response to iNO in preterm infants with respiratory failure. METHODS: This is a retrospective study of 17 preterm infants with respiratory failure whose birth weight were 1,250 g or less and were treated with iNO, admitted in the neonatal intensive care units at Seoul National University Bundang Hospital between January 2006 and June 2010. Infants were classified as responders if they presented a reduction of FiO2 of more than 20% during 24 hours from the beginning of the treatment, and as non-responder if not. RESULTS: Eight infants (47%) were classified as the responder group and nine infants (53%) as the non-responder group. Mean gestational age was 25.4+/-1.6 weeks in the responder group and 26.0+/-1.6 weeks in the non-responder group. Mean birth weight was 701.9+/-190.1 g in the responder group and 816.1+/-241.6 g in the non-responder group. In the responder group, infants received iNO at postnatal day 12+/-9, in the non-responder group, iNO at postnatal day 35+/-25 (P=0.02). The exposure duration to FiO2 > or =0.5 prior to iNO treatment was significantly shorter in responders than in non-responders (0.1+/-0.4 d vs. 12.6+/-16.3 d, P=0.04). The mechanical ventilation duration was shorter and the postmenstrual age and postnatal age at last extubation were earlier in responders than in non-responders (52+/-25 d vs. 120+/-67 d, P=0.03) (33.1+/-3.0 weeks vs. 45.4+/-9.5 weeks, P=0.01; 55+/-25 d vs. 125+/-59 d, P=0.01). The postmenstrual age and postnatal age at last oxygen treatment were earlier in responders than in non-responders (41.1+/-2.4 weeks vs. 49.0+/-4.5 weeks, P=0.03; 109+/-28 d vs. 158+/-36 d, P=0.03). CONCLUSION: Responders during iNO treatment in preterm infants with respiratory failure had earlier postnatal age and shorter duration of the exposure to hyperoxia. The responder group resulted in good response with early iNO treatment, thus the weaning of mechanical ventilation and oxygen was earlier than the non-responder group. Further studies on effects of beginning time of iNO treatment and long-term effects, especially bronchopulmonary dysplasia, intraventricular hemorrhage and neurodevelopmental outcome are necessary.

Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn (PPHN) is defined as a failure of normal pulmonary vascular relaxation at or shortly after birth, resulting in impedance to pulmonary blood flow which exceeds systemic vascular resistance, such that unoxygenated blood is shunted to the systemic circulation. Perinatal stressors including hypoxia, hypoglycemia, cold stress, sepsis, and direct lung injury alter the course of transition. The initial clinical picture of PPHN is one of dynamic pulmonary vasospasm, with labile flow through the pulmonary circuit and right-to-left shunting of blood across the ductus arteriosus and foramen ovale. The normal postnatal decline in pulmonary vascular tone is absent following exposure to chronic hypoxia. The pathophysiology of neonatal pulmonary hypertension can involve multiple pathways of injury, from altered circulating agonist balance, to endothelial dysfunction, to smooth muscle dysfunction and phenotypic change. The treatment for PPHN has evolved over the past 10 to 15 years but reported mortality remains at 10% to 20% in newborns with PPHN. Extracorporeal membrane oxygenation (ECMO) has been proven of value for this condition, and several "alternative" therapies such as high-frequency ventilation (HFV), surfactant, and inhaled NO (iNO) have been used in a rescue mode.

Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn (PPHN) is defined as a failure of normal pulmonary vascular relaxation at or shortly after birth, resulting in impedance to pulmonary blood flow which exceeds systemic vascular resistance, such that unoxygenated blood is shunted to the systemic circulation. Perinatal stressors including hypoxia, hypoglycemia, cold stress, sepsis, and direct lung injury alter the course of transition. The initial clinical picture of PPHN is one of dynamic pulmonary vasospasm, with labile flow through the pulmonary circuit and right-to-left shunting of blood across the ductus arteriosus and foramen ovale. The normal postnatal decline in pulmonary vascular tone is absent following exposure to chronic hypoxia. The pathophysiology of neonatal pulmonary hypertension can involve multiple pathways of injury, from altered circulating agonist balance, to endothelial dysfunction, to smooth muscle dysfunction and phenotypic change. The treatment for PPHN has evolved over the past 10 to 15 years but reported mortality remains at 10% to 20% in newborns with PPHN. Extracorporeal membrane oxygenation (ECMO) has been proven of value for this condition, and several "alternative" therapies such as high-frequency ventilation (HFV), surfactant, and inhaled NO (iNO) have been used in a rescue mode.

A Case of Bilateral Internuclear Ophthalmoplegia with No Brain Stem Lesion

PURPOSE: Bilateral internuclear ophthalmoplegia (INO) has been reported mostly in bilateral medial longitudinal fasciculus (MLF) lesion. To report a case who presented with typical bilateral internuclear ophthalmoplegia (INO) with no brainstem lesion on brain MRI. METHODS: Case presentation. RESULTS: Seventy two year-old woman presented with bilateral marked adduction limitation and diplopia. Bilateral marked adduction limitation did not cross midline. Nystagmus occured in abducting eye. Elevation and depression were normal in duction. Transcranial doppler revealed moderated stenosis of right internal carotid artery and severe stenosis of left intracranial internal carotid artery. Brain MRI revealed focal old infarction of right corona radiata and circumscribed acute infarction at more upper level of corona radiata, however, no pathologic finding was identified in brainstem. Initial severe exotropia was improved to 30 PD exotropia in primary position. Adduction limitation was markedly improved 2 months later but bilateral horizontal nystagmus in abducting eye persisted

Cheiro-oral Syndrome with INO following Brainstem Infarction

Brainstem lesions may produce a cheiro-oral syndrome infrequently. The cheiro-oral syndrome in pontine lesion is due to involvement of ventral trigeminothalamic tract and the medial part of the medial lemniscus. The cheiro-oral syndrome rarely associates with internuclear ophthalmoplegia. A 58-year-old hypertensive man complained of dizziness, diplopia, and dysesthesia in the right hand and ipsilateral perioral region. On neurologic examination, there was left internuclear ophthalmoplegia. Others were unremarkable. Brain MRI demonstrated a small round lesion in the paramedian tegmentum of the left upper pons and lower midbrain, which involved ventral trigeminothalamic tract, medial part of medial lemniscus and medial longitudinal fasciculus. We report a case of brainstem infarction with a rare combination of cheiro-oral syndrome and internuclear ophthalmoplegia.

THE DETERMINATION OF SOME NUTRITIONAL ELEMENTS IN ABALONE HALIOTIS DISCUS HANNAI INO / 中国海洋药物

This paper reported protein (50. 81%),rude fat (6. 24%),amio acids and mineral elements of abalone Haloitis discus hannai. And the shell and meat of the abalone for medical use was also introduced.

MR imaging of internuclear ophthalmoplegia due to cerebrovascular diseases / 영남의대학술지

Internuclear ophthalmoplegia is a conjugated gaze disorder characterized by impaired adduction on the side of a lesion involving the medial longitudinal fasciculus with dissociated nystagmus of the other abducting eye. Six patients with INO (who had clinical cerebrovascular diseases) underwent MR imaging and the results were as follows: 1. The MLF lesions were identified by MR imaging in 5 cases 2. The ratio of unilateral INO to bilateral INO was 5:1 3. The nature of lesions was infarction in 4 cases and hemorrhage in 1 case 4. The sites of MLE lesion were in the midbrain in 4 cases and in the pons in 1 case 5. All 5 cases of INO identified by MR imaging had other lesion sites in addition to MLE lesion.

Study on mechanism of D- amino acid oxidase/D- Alanine system on killing K5 62 e cell in vitro / 第二军医大学学报

Objective:To investigate the m echanism of D- amino acid oxidase/D- Alanine system in killing K5 6 2 e cells in vitro.Methods:The killing effects of D- Ala on K5 6 2 e cells stably expressing DAAO and GFP were observed.H2 O2 production by DAAO+ cells were m easured by the phenol red oxidation assay.L owry method was used to determ ine the protein quantities of cells and fluorescent intensities of GFP+ cells were assayed by flow cytom eter.Results:KDf Gd cells were killed completely after treated with 2 5 mm ol/L D- Ala for 2 4 h.The effect of D - Ala at 2 0 m mol/L on KDf Gd cells increased apparently within 4 8h,but the same effect was not observed if D - Ala was below 15 m mol/L .The cytotoxicity of D- Ala in KDf Gd cells was more sensitive than in parental K 5 6 2 e cells.The H2 O2 levels in the medium were consistent with the killing effects of D- Ala.Conclusion:The killing effects of DAAO/D- Ala system is m ediated by H2 O2 . [