78 research outputs found
Cardiovascular Health in Kawasaki Disease
Kawasaki disease (KD) is a self-limiting vasculitis of unknown etiology primarily affecting young children. The most important aspect in the treatment of KD is the prevention of coronary artery lesions (CALs) because myocardial ischemia or infarction due to coronary artery stenosis or occlusion may be lethal. In addition, patients with a history of KD have systemic vasculitis, which indicates vascular endothelial damage. Therefore, patients with CAL are at a high risk of atherosclerosis. While some reports have shown an increase in vascular stiffness, others have not, and the presence of atherosclerotic lesions in patients with KD is controversial. Appropriate acute-phase treatment to prevent CAL and systemic vasculitis and subsequent regular follow-ups are important. This chapter deals with the cardiovascular health of patients with a history of KD
Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes.
Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part
Stent Implantation for Effective Treatment of Refractory Chylothorax due to Superior Vena Cava Obstruction as a Complication of Congenital Cardiac Surgery
Chylothorax is a serious complication of congenital cardiac surgery and is significantly associated with increased morbidity and mortality. Central venous obstruction, which is often related to the insertion of central venous catheters for postoperative management, is known to be an important risk factor for treatment failure and mortality associated with this condition. We present the case of a 6-month-old girl with refractory chylothorax after surgical repair of tetralogy of Fallot. The chylous drainage continued for more than 2 months despite maximal conservative therapy (water restriction, total parenteral nutrition, and infusion of somatostatin and steroid) and surgical ligation of the thoracic duct. Subsequently, we observed stenosis of the superior vena cava (SVC) caused by large thrombi possibly associated with the prolonged use of central venous catheter placed in the internal jugular vein. Because transcatheter balloon dilation failed to relieve the stenosis, we performed stent implantation for the SVC and innominate vein. After the procedure, chylous drainage dramatically reduced, and the patient was discharged from the hospital. In conclusion, central venous obstruction due to thrombosis should be routinely examined when chylothorax is diagnosed and is resistant to conservative therapy after congenital heart surgery. Stent implantation can effectively relieve the venous obstruction and thus be a life-saving treatment option for this difficult condition
Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension
Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening
High Serum Levels of Procollagen Type III-N-terminal Amino Peptide in Patients with Congenital Heart Disease
Abstract Objective: The serum concentration of amino-terminal procollagen type III (PIIIP) is considered a useful marker of tissue fibrogenesis. The present study tested the hypothesis that: 1) serum PIIIP levels are elevated in patients with congenital heart disease (CHD) and abnormal hemodynamic loading and/or hypoxemia, 2) PIIIP levels are associated with severity of hemodynamic load or hypoxemia, both of which enhance myocardial fibrosis. Methods and Results: Serum PIIIP levels were measured in 5 groups of CHD patients [42 patients with ventricular septal defect (VSD), 26 with coarctation of the aorta (COA, n=19) or aortic stenosis (AS, n=7), 36 with atrial septal defect (ASD), 39 with pulmonary stenosis (PS) and 20 with tetralogy of Fallot (TOF)]. PIIIP levels of CHD patients were significantly higher than those of 42 control subjects (p<0.05, each). Serum PIIIP levels increased in parallel with increased ventricular volume load in VSD and ASD, and with severity of PS. In TOF patients, PIIIP levels correlated negatively with arterial oxygen saturation. Treatment with angiotensin converting enzyme inhibitor (ACEI) was associated with low levels of PIIIP in COA/AS patients despite existing hemodynamic load. Conclusion: The increased serum PIIIP levels in proportion with the severity of ventricular load or cyanosis suggest enhanced myocardial synthesis of collagen type III in patients with CHD. Suppression of PIIIP level by ACEI suggests the involvement of the renin-angiotensin-aldosterone system in myocardial fibrosis. These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with CHD
Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit
Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.
横紋筋肉腫におけるゲノム・エピゲノム異常の全体図を解明 -横紋筋肉腫を4群に分類-. 京都大学プレスリリース. 2015-07-03.Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS
Coincidence analysis to search for inspiraling compact binaries using TAMA300 and LISM data
Japanese laser interferometric gravitational wave detectors, TAMA300 and
LISM, performed a coincident observation during 2001. We perform a coincidence
analysis to search for inspiraling compact binaries. The length of data used
for the coincidence analysis is 275 hours when both TAMA300 and LISM detectors
are operated simultaneously. TAMA300 and LISM data are analyzed by matched
filtering, and candidates for gravitational wave events are obtained. If there
is a true gravitational wave signal, it should appear in both data of detectors
with consistent waveforms characterized by masses of stars, amplitude of the
signal, the coalescence time and so on. We introduce a set of coincidence
conditions of the parameters, and search for coincident events. This procedure
reduces the number of fake events considerably, by a factor
compared with the number of fake events in single detector analysis. We find
that the number of events after imposing the coincidence conditions is
consistent with the number of accidental coincidences produced purely by noise.
We thus find no evidence of gravitational wave signals. We obtain an upper
limit of 0.046 /hours (CL ) to the Galactic event rate within 1kpc from
the Earth. The method used in this paper can be applied straightforwardly to
the case of coincidence observations with more than two detectors with
arbitrary arm directions.Comment: 28 pages, 17 figures, Replaced with the version to be published in
Physical Review
Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004
We analyze the data of TAMA300 detector to search for gravitational waves
from inspiraling compact star binaries with masses of the component stars in
the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the
years 2000-2004, are used for the event search. We combine the results of
different observation runs, and obtained a single upper limit on the rate of
the coalescence of compact binaries in our Galaxy of 20 per year at a 90%
confidence level. In this upper limit, the effect of various systematic errors
such like the uncertainty of the background estimation and the calibration of
the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was
correcte
Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses
We present data-analysis schemes and results of observations with the TAMA300
gravitational-wave detector, targeting burst signals from stellar-core collapse
events. In analyses for burst gravitational waves, the detection and
fake-reduction schemes are different from well-investigated ones for a
chirp-wave analysis, because precise waveform templates are not available. We
used an excess-power filter for the extraction of gravitational-wave
candidates, and developed two methods for the reduction of fake events caused
by non-stationary noises of the detector. These analysis schemes were applied
to real data from the TAMA300 interferometric gravitational wave detector. As a
result, fake events were reduced by a factor of about 1000 in the best cases.
The resultant event candidates were interpreted from an astronomical viewpoint.
We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave
event rate in our Galaxy with a confidence level of 90%. This work sets a
milestone and prospects on the search for burst gravitational waves, by
establishing an analysis scheme for the observation data from an
interferometric gravitational wave detector
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