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Biomedical subjects

Ikuo Hashimoto

Publications and source records attributed to Ikuo Hashimoto.

18 recordsLinked to original sources
PubMed2006

Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease.

OBJECTIVES: This study investigated patients with acute Kawasaki disease (KD) to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development. BACKGROUND: Both MRP-8 and -14, which are S100-proteins secreted by activated neutrophils and monocytes, bind specifically to endothelial cells and induce thrombogenic and inflammatory responses in a variety of disease conditions. METHODS: We investigated 61 patients with acute KD and examined sequential changes in serum levels of MRP-8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to circulating endothelial cells. RESULTS: The serum MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated during the early stage of acute KD, and decreased dramatically within 24 h of intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in 16 nonresponders both of these increased after the initial treatment. The number of MRP-8/MRP-14-positive circulating endothelial cells was higher in patients with acute KD than in control patients and increased significantly by 2 weeks after the onset of KD, especially in patients in whom coronary artery lesions developed. CONCLUSIONS: We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KD, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14-positive circulating endothelial cell may predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.

Acute Disease↗
PubMed2006

Open heart operation in a child with congenital heart disease and hereditary spherocytosis.

An 18-month-old girl with hereditary spherocytosis underwent closure of the ventricular septal defect, commissurotomy of the pulmonary valve, and patch angioplasty of the pulmonary trunk without previous splenectomy. No serious complications as a result of hemolysis occurred in the perioperative period. Open heart surgery can therefore be safely performed in young children with congenital heart disease and hereditary spherocytosis who have not previously undergone splenectomy.

Female↗
PubMed2004

Tissue Doppler-derived myocardial acceleration for evaluation of left ventricular diastolic function.

OBJECTIVES: Our purpose was to evaluate a tissue Doppler-based index-peak myocardial acceleration (pACC)-during isovolumic relaxation and in evaluating left ventricular (LV) diastolic function. BACKGROUND: Simple, practical indexes for diastolic function evaluation are lacking, but are much desired for clinical evaluation. METHODS: We examined eight sheep by using tissue Doppler ultrasound images obtained in the apical four-chamber views to evaluate mitral valve annular velocity at the septum and LV wall. The pACC thus derived was analyzed during isovolumic relaxation (IVRT) and during the LV filling period (LVFP). We then changed the hemodynamic status of each animal by blood administration, dobutamine, and metoprolol infusion. We compared the pACC values during IVRT and LVFP over the four different hemodynamic conditions with a peak rate of drop in LV pressure (-dP/dt(min)) and the time constant of LV isovolumic pressure decay (tau), as measured with a high-frequency manometer-tipped catheter. RESULTS: The pACC of the septal side of the mitral valve annulus during IVRT showed a good correlation with -dP/dt(min) (r = -0.80, p < 0.0001) and tau (r = -0.87, p < 0.0001). The mean left atrial pressure (LAP) correlated well with the septal side pACC during LVFP (r = 0.81, p < 0.0001). There was a weak correlation between the mitral valve annulus pACC at the LV lateral wall and mean LAP. CONCLUSIONS: The pACC during IVRT is a sensitive, preload-independent marker for evaluation of LV diastolic function. In addition, pACC during LVFP correlated well with mean LAP.

Animals↗
PubMed2004

Neutrophil-derived S100A12 is profoundly upregulated in the early stage of acute Kawasaki disease.

Neutrophil-derived S100A12 is strongly upregulated during the acute stage of Kawasaki disease and decreases significantly in response to intravenous immune globulin (IVIG) treatment, whereas in nonresponders, serum concentrations increases after initial treatment. Decreased S100A12 expression in neutrophils was detected initially in nonresponders but increased significantly after IVIG treatment, suggesting delayed inflammatory response of neutrophils in nonresponders. Furthermore, in vitro S100A12 secretion increased with tumor necrosis factor-alpha (TNF-alpha) stimulation, whereas intracellular levels were lower in neutrophils with the higher TNF-alpha dose, suggesting intracellular depletion. S100A12 expression in neutrophils appears to reflect responsiveness to IVIG treatment and is possibly involved in the pathophysiology of acute vasculitis.

Acute Disease↗
PubMed2004

Histone deacetylase inhibitor, FK228, induces apoptosis and suppresses cell proliferation of human glioblastoma cells in vitro and in vivo.

We investigated the effects of FK228 on cell proliferation and apoptosis against human glioblastoma (GM) T98G, U251MG, and U87MG cells. Upon exposure to FK228, cell proliferation was inhibited, and apoptosis detected by the cleavage of CPP32 was induced. FK228 increased the expression levels of p21 (WAF-1) and of pro-apoptotic Bad protein in all GM cells. Furthermore, FK228 treatment also reduced the anti-apoptotic protein Bcl-xL in all GM cells and anti-apoptotic Bcl-2 in U87MG cells, thereby shifting the cellular equilibrium from life to death. An increased accumulation of histone H4 was detected in the p21 (WAF-1) promoter and the structural gene (exon 2) and the Bad structural gene (exon 2 and 3) upon treatment with FK228, as assessed by chromatin immunoprecipitation (ChIP) assay. Thus, the results indicated that an increased expression of p21 (WAF1) and Bad due to FK228 is regulated, at least in part, by the degree of acetylation of the gene-associated histone. We also found that FK228 inhibits cellular invasiveness and decreases MMP-2 activity. In addition, the growth of transplanted human GM m-3 cells into the subcutaneous tissue of hereditary athymic mice was significantly inhibited, and apoptosis was induced with FK228 treatment. The results suggested that FK228 might be useful in the treatment of human GM, although further studies will be needed.

Animals↗
PubMed2004

Enhanced iNOS expression in leukocytes and circulating endothelial cells is associated with the progression of coronary artery lesions in acute Kawasaki disease.

Nitric oxide (NO) serves many vasoprotective roles, but the massive release of NO causes arterial wall degeneration. We investigated whether enhanced nitric oxide synthase (iNOS) expression in peripheral blood leukocytes and circulating endothelial cells mirrors the progression of coronary arterial lesions in 55 children with acute Kawasaki disease (KD), including 24 with and 31 without coronary artery lesions (CAL). Patients were treated with i.v. gamma-globulin at the time of diagnosis and blood samples were collected before and after treatment. The cellular origin of NO synthesis was determined by flow cytometric analysis of iNOS expression in peripheral blood, and by immunohistochemical analysis of circulating endothelial cells and coronary arteries. iNOS expression in neutrophils peaked at the time of diagnosis, but did not peak in monocytes until 2 wk post onset of disease. Levels were significantly higher in both cell types in patients with CAL (p = 0.001 and p = 0.035, respectively). In addition, the number of circulating endothelial cells and levels of iNOS expression were higher in patients with CAL (p = 0.011 and p = 0.012, respectively). Immunohistochemical analysis of the coronary arteries from three patients with acute KD revealed iNOS immunoreactivity in endothelial cells, as well as infiltrating monocytes/macrophages in the aneurysms. We conclude that the expression of iNOS in peripheral blood leukocytes, as well as circulating endothelial cells, correlates with the severity of coronary arterial wall injury and the progression of CAL in patients with acute KD.

Arteries↗
PubMed2004

Real-time 3-dimensional echocardiography for quantification of the difference in left ventricular versus right ventricular stroke volume in a chronic animal model study: Improved results using C-scans for quantifying aortic regurgitation.

OBJECTIVE: The purpose of our study was to test the applicability of calculating the difference between left ventricular (LV) and right ventricular (RV) stroke volume (SV) for assessing the severity of aortic (Ao) regurgitation (AR) using a real-time 3-dimensional (3D) echocardiographic (RT3DE) imaging system. METHODS: The Ao valve was incised in 5 juvenile sheep, 6 to 10 weeks before the study, to produce AR (mean regurgitant fraction = 0.50). Simultaneous hemodynamic and RT3DE images were obtained on open-chest animals with Ao and pulmonary flows derived by Ao and pulmonary electromagnetic flowmeters balanced against each other. Four stages (baseline, volume loading, sodium nitroprusside, and angiotensin infusion) were used to produce a total of 16 different hemodynamic states. Epicardial scanning was done with a 2.5-MHz probe to sequentially record first the RV and then the LV cavities. Cavity volumes from the 3D echocardiography data were determined from angled sector planes (B-scans) and parallel cutting planes (C-scans, which are planes perpendicular to the direction of the volume interrogation). AR volumes were determined from 3D images by computing and then subtracting RV SVs from LV SVs and then these were compared with electromagnetic flowmeter-derived SV and regurgitant volumes. RESULTS: There was close correlation between RV and LV SVs of the RT3DE and electromagnetic methods (C-scans: LV, r = 0.98, standard error of the estimate [SEE] = 2.62 mL, P =.0001; RV, r = 0.89, SEE = 2.67 mL, P <.0001; and B-scans: LV, r = 0.95, SEE = 3.55 mL, P =.0001; RV, r = 0.77, SEE = 2.78 mL, P =.0003). Because of the small size of the RV in this model, the correlation was closer for C-scans than B-scans for RV SV. AR volume estimation also showed that C-scan (r = 0.93, SEE = 4.23 mL, P <.0001) had closer correlation than B-scan (r = 0.89, SEE = 4.87 mL, P <.0001). However, B-scan-derived AR fraction showed closer correlation than did C-scan (r = 0.82 vs r = 0.85, respectively). CONCLUSION: In this animal model, RT3DE imaging had the ability to reliably quantify both LV (B- and C-scans) and RV SVs and to assess the severity of AR.

Animals↗
PubMed2004

Determination of asymmetric cavity volumes using real-time three-dimensional echocardiography: an in vitro balloon model study.

OBJECTIVES: We designed a new in vitro model to test the accuracy and reproducibility of real-time three-dimensional (RT3D) ultrasound imaging for determining a variety of asymmetric cavity volumes with aneurysm. METHODS: Fifteen individual balloon models mimicking ventricular aneurysm were filled with water (170-322.5 ml) without air bubbles and kept in a compressor pump. Compression of the models produced only a change in shape of the balloon and no change in volume. The models were scanned with RT3D echocardiography (RT3DE) and the images recorded on an optical disk. Volumes were measured off line in two phases; maximal compression, where there was maximal change in shape and nil compression, where there was minimal or no change in shape. Volumes were measured by manual tracing technique of the inner border of B-scan images and compared with the drained volume of water from the balloon. RESULTS: There was a high correlation between the drained volume and measured volume at maximal compression (equivalent to end-systole, r = 0.99, y = 0.99x + 3.69, SEE = 6.5 ml), between the drained volume and measured volume at nil compression (equivalent to end-diastole, r = 0.99, y = 0.94x + 12.07, SEE = 5.9 ml), and between volumes measured at maximal and nil compressions (r = 0.99, y = 0.94x + 10.55, SEE = 4.6 ml). CONCLUSION: The results of this experiment show that RT3DE can accurately measure the volumes of a variety of asymmetric ventricular cavities.

Cardiac Volume↗
PubMed2004

Cusp extension technique for bicuspid aortic valve in Turner-like stigmata.

A 19-year-old girl with bicuspid aortic valve and Turner-like stigmata underwent a successful repair with a cusp extension technique using fresh autologous pericardium for aortic insufficiency. She also had a simultaneous artificial graft replacement for ascending aortic dilatation. Aortic valve function showed no significant stenosis and slight insufficiency 2 years postoperatively. This technique is recommended to avoid a Ross or Ross/Konno procedure because of its ready availability, simplicity and excellent midterm results.

Adult↗
PubMed2003

Myocardial strain rate is a superior method for evaluation of left ventricular subendocardial function compared with tissue Doppler imaging.

OBJECTIVES: This study was performed to evaluate subendocardial function using strain rate imaging (SRI). BACKGROUND: The subendocardium and mid-wall of the left ventricle (LV) play important roles in ventricular function. Previous methods used for evaluating this function are either invasive or cumbersome. Strain rate imaging by ultrasound is a newly developed echocardiographic modality based on tissue Doppler imaging (TDI) that allows quantitative assessment of regional myocardial wall motion. METHODS: We examined eight sheep using TDI in apical four-chamber views to evaluate the LV free wall. Peak strain rates (SRs) during isovolumic relaxation (IR), isovolumic contraction (IC), and myocardial strain were measured in the endocardial (End), mid-myocardial (Mid), and epicardial (Epi) layers. For four hemodynamic conditions (created after baseline by blood, dobutamine, and metoprolol infusion), we compared differences in SR of End, Mid, and Epi layers to peak positive and negative first derivative of LV pressure (dP/dt). RESULTS: Strain rate during IC showed a good correlation with +dP/dt (r = 0.74, p < 0.001) and during IR with -dP/dt (r = 0.67, p = 0.0003). There was a significant difference in SR between the myocardial layers during both IC and IR (End: -3.4 +/- 2.2 s(-1), Mid: -1.8 +/- 1.5 s(-1), Epi: -0.63 +/- 1.0 s(-1), p < 0.0001 during IC; End: 2.2 +/- 1.5 s(-1), Mid: 1.0 +/- 0.8 s(-1), Epi: 0.47 +/- 0.64 s(-1), p < 0.0001 during IR). Also, SRs of the End and Mid layers during IC were significantly altered by different hemodynamic conditions (End at baseline: 1.7 +/- 0.7 s(-1); blood: 2.0 +/- 1.1 s(-1); dobutamine: 3.4 +/- 2.3 s(-1); metoprolol: 1.0 +/- 0.4 s(-1); p < 0.05). Myocardial strain showed differences in each layer (End: -34.3 +/- 12.6%; Mid: -22.6 +/- 12.1%; Epi: -11.4 +/- 7.9%; p < 0.0001) and changed significantly in different hemodynamic conditions (p < 0.0001). CONCLUSIONS: Strain and SR appear useful and sensitive for evaluating myocardial function, especially for the subendocardial region.

Animals↗
PubMed2003

Transannular patching for tetralogy of Fallot with an anomalous right coronary artery.

A 7-year-old girl underwent transannular patching under the mobilized anomalous right coronary artery across the right ventricular outflow to treat progressing infundibular stenosis 6 years after total repair of the tetralogy of Fallot. The procedure completely relieved recurrent stenosis. Simultaneous angiography of the coronary artery and right ventricle were useful in precisely evaluating coronary anatomy.

Child↗
PubMed2003

A case of congenital midline cervical cleft with congenital heart disease.

A congenital midline cervical cleft (CMCC) is a rare developmental anomaly. It may represent failure of the branchial arches to fuse in the midline and presents at birth with a ventral midline defect of the skin of the neck. Congenital heart disease along with CMCC is rarer, and most of the cases reported are associated with chest wall defects or thoracic ectopia cordis. The authors report a case of a 5-month-old girl with CMCC and an atrial septal defect (ASD) and discuss the clinical presentation, embryologic development, and treatment.

Abnormalities, Multiple↗
PubMed2003

Strain rate acceleration yields a better index for evaluating left ventricular contractile function as compared with tissue velocity acceleration during isovolumic contraction time: an in vivo study.

OBJECTIVE: Our study aimed to investigate whether strain rate acceleration (SRA) during isovolumic contraction time (IVCT) could serve as a sensitive indicator of myocardial function. METHODS: A total of 8 sheep underwent occlusion of left anterior descending coronary artery or diagonal branches and 2 sheep underwent left circumflex coronary artery occlusion to create septal, apical, or basal segment myocardial ischemia 19 to 27 weeks before the study. Baseline, volume-loading, dobutamine, and metoprolol infusion were used to produce 4 hemodynamic stages for each sheep. Doppler tissue imaging was acquired using a 5-MHz probe (GE/VingMed Vivid Five, GE Medical Systems, Milwaukee, Wis) on open-chest animals using the liver as a standoff at the apex. Using software (EchoPac, GE Medical Systems), SRA during IVCT was calculated and compared with tissue velocity acceleration (TVA) during IVCT from areas located in the normal and ischemic zones. Also, invasively monitored left ventricle dP/dt was measured as reference contractile function. RESULTS: Both TVA and SRA during IVCT showed higher values for normal tissue than for ischemic area (P <.0001). SRA for normal wall segments changed significantly during the 4 stages (P =.01) with corresponding changes on high-fidelity left ventricular pressure catheters (r = 0.92). TVA over normal segments showed no significant change (P =.29) in the 4 hemodynamic stages. Both TVA and SRA of the ischemic segments showed no significant change with pharmacologic maneuvers or loading conditions. CONCLUSIONS: SRA and TVA during IVCT are both useful indicators for detecting abnormal heart wall motion. However, SRA tends to be more sensitive than TVA for differentiating the response to stress conditions.

Animals↗
PubMed2002

Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells.

We investigated the effects of histone deacetylase (HDAC) inhibitors such as sodium butyrate (SB) and trichostatin A (TSA) on the expression of vascular endothelial growth factor (VEGF) by human glioblastoma T98G, U251MG, and U87MG cells. The glioblastoma cells secreted three VEGF isoforms, VEGF (189), (165), and (121), although the expression levels of VEGF differed between the cell types. Treatment with either 5mM SB or 100 ng/ml TSA reduced VEGF secretion in conditioned media and reduced VEGF mRNA expression. We also studied the expression of VEGF-B, -C, and -D mRNA in human glioblastoma cells and their modulation by HDAC inhibitors. The PCR products of VEGF-B (357bp), VEGF-C (501bp), and VEGF-D (484bp) were amplified in all glioblastoma cells examined. Treatment with SB reduced the expression of VEGF-D mRNA in U251MG cells and the expression of VEGF-B mRNA in U87MG cells. TSA treatment reduced the expression of VEGF-D in U251MG cells. These results suggest that HDAC inhibitors reduce VEGF secretion and modulate the expression of the other VEGF family members, and therefore may inhibit angiogenesis in glioblastoma tissues.

Blotting, Western↗
PubMed2002

Strain rate imaging: an in vitro "validation" study using a physiologic balloon model mimicking the left ventricle.

BACKGROUND: Strain rate imaging (SRI) can be implemented from digital ultrasound loops of tissue Doppler imaging (TDI) data and is performed as an autocorrelation solution of the distance between intramyocardial targets. As such, it should have better resolution along longer distances of wall segments that are imaged at the length of individual ultrasound scan lines. METHODS: We used a new left ventricular double-balloon phantom with a tissue-mimicking gel between the walls. Mounted in a water bath and connected to a pulsatile flow pump at four-stroke volume (30-50 ml/beat), the high frame rate, digital, multiple two-dimensional/tissue/TDI loops of balloon wall motion were recorded using a GE VingMed system FiVe (3.5 MHz phased array transducer), with the model scanned longitudinally from the apex. The strain rate (SR) values were measured at the apex and the lateral wall using an offline measurement program, and mean SR values for every 100 msec were calculated by averaging three determinations at each point. The excursions of the apex and lateral wall also were measured directly by high speed digital video imaging, and consecutive velocity profiles were calculated every 100 msec. A total of 40 data points for four-stroke volumes were analyzed. RESULTS: While our balloon model had enough gel targets between the walls to produce a good mimic of myocardial speckle with walls that thickened and thinned, samples immediately across the apex and apex SR values (Hz) varied substantially. In contrast, systematic signals could be obtained from lines imaged >15 degrees from the true apex and crossing a longer length of myocardium. At the lateral wall, there was a close correlation between the video velocities and SR values, as well as a close overlap of the phasic patterns. CONCLUSIONS: SRI produces more reliable data from wall segments parallel to scan lines.

Blood Flow Velocity↗
PubMed2002

Quantification of instantaneous flow rate and dynamically changing effective orifice area using a geometry independent three-dimensional digital color Doppler method: An in vitro study mimicking mitral regurgitation.

OBJECTIVE: Our study was intended to test the accuracy of a 3-dimensional (3D) digital color Doppler flow convergence (FC) method for assessing the effective orifice area (EOA) in a new dynamic orifice model mimicking a variety of mitral regurgitation. BACKGROUND: FC surface area methods for detecting EOA have been reported to be useful for quantifying the severity of valvular regurgitation. With our new 3D digital direct FC method, all raw velocity data are available and variable Nyquist limits can be selected for computation of direct FC surface area for computing instantaneous flow rate and temporal change of EOA. METHODS: A 7.0-MHz multiplane transesophageal probe from an ultrasound system (ATL HDI 5000) was linked and controlled by a computer workstation to provide 3D images. Three differently shaped latex orifices (zigzag, arc, and straight slit, each with cutting-edge length of 1 cm) were used to mimic the dynamic orifice of mitral regurgitation. 3D FC surface computation was performed on parallel slices through the 3D data set at aliasing velocities (14-48 cm/s) selected to maximize the regularity and minimize lateral dropout of the visualized 3D FC at 5 points per cardiac cycle. Using continuous wave velocity for each, 3D-calculated EOA was compared with EOA determined by using continuous wave Doppler and the flow rate from a reference ultrasonic flow meter. Simultaneous digital video images were also recorded to define the actual orifice size for 9 stroke volumes (15-55 mL/beat with maximum flow rates 45-182 mL/s). RESULTS: Over the 9 pulsatile flow states and 3 orifices, 3D FC EOAs (0.05-0.63 cm(2)) from different phases of the cardiac cycle in each pump setting correlated well with reference EOA (r = 0.89-0.92, SEE = 0.027-0.055cm(2)) and they also correlated well with digital video images of the actual orifice peak (r = 0.97-0.98, SEE = 0.016-0.019 cm(2)), although they were consistently smaller, as expected by the contraction coefficient. CONCLUSION: The digital 3D FC method can accurately predict flow rate, and, thus, EOA (in conjunction with continuous wave Doppler), because it allows direct FC surface measurement despite temporal variability of FC shape.

Blood Flow Velocity↗
PubMed2002

Dobutamine stress radionuclide ventriculography reveals silent myocardial dysfunction in Kawasaki disease.

Dobutamine (DOB) stress radionuclide ventriculography (RVG) is proposed for evaluating left ventricular performance in patients with Kawasaki disease (KD). Dobutamine stress RVG, up to 15 microg x kg(-1) x min(-1), was performed in 40 patients with a history of KD, some of whom had a perfusion defect (PD group) on dipyridamole stress thallium-201 myocardial imaging, some of whom had no perfusion defects (NPD group), and some of whom had no coronary artery lesions (C group). No significant differences in either systolic or diastolic indices of the left ventricle at rest were observed between the 3 groups. Although hemodynamic responses were similar in all patients after DOB stress, early diastolic index of the first third filling fraction decreased only in the PD group and was significantly lower in this group compared with the C group (p<0.01). The asynchrony index increased significantly in those patients with coronary stenosis after DOB stress (p<0.05). No serious side-effects were observed during the study. Even late after onset, patients with myocardial ischemia as a result of KD still had impaired early diastolic filling and asynchronous relaxation of the left ventricle. As an alternative to exercise testing, DOB stress RVG is a safe and promising means for serially evaluating left ventricular performance in patients with KD.

Adolescent↗