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Biomedical subjects

Yuichi Ueda

Publications and source records attributed to Yuichi Ueda.

At least 37 records · Page 2Linked to original sources

Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer.

Secreted frizzled related protein 1 (SFRP 1) is an antagonist of the transmembrane frizzled receptor, a component of the Wnt signaling pathway, and has been suggested to be a candidate tumor suppressor in several human malignancies. Since SFRP 1 is located at chromosome 8 p 11, where lung cancers also exhibit frequent allelic loss, we hypothesized that the inactivation of SFRP 1 is also involved in lung carcinogenesis. To substantiate this, we performed mutational analysis of SFRP 1 for 29 non-small-cell lung cancer (NSCLC) and 25 small-cell lung cancer (SCLC) cell lines, and expression analysis for the same cell lines. Although somatic mutations were not detected in the coding sequence, downregulation of SFRP 1 was observed in 14 (48%) NSCLC and nine (36%) SCLC cell lines. We analysed epigenetic alteration of the SFRP 1 promoter region and detected hypermethylation in 15 (52%) of 29 NSCLC cell lines, two (8%) of 25 SCLC cell lines, and 44 (55%) of 80 primary lung tumors. By comparing the methylation status with SFRP 1 expression, we found a significant correlation between them. We also performed loss of heterozygosity (LOH) analysis and found that 15 (38%) of 40 informative surgical specimens had LOH in the SFRP 1 gene locus. Furthermore, we performed colony formation assay of two NSCLC cell lines (NCI-H 460 and NCI-H 2009) and found the reduction of colony formation with SFRP 1 transfection. In addition, we also detected that SFRP 1 inhibits the transcriptional activity of beta-catenin, which is thought to be a downstream molecule of SFRP 1, with luciferase reporter assay. Our current studies demonstrated that the SFRP 1 gene is frequently downregulated by promoter hypermethylation and suppresses tumor growth activity of lung cancer cells, which suggests that SFRP 1 is a candidate tumor suppressor gene for lung cancer.

Base Sequence↗

Temperature dependent emission of hexarhenium(III) clusters [Re6(mu3-S)8X6]4- (X = Cl-, Br-, and I-): analysis by four excited triplet-state sublevels.

Temperature (T) dependences of the emission spectra and lifetimes of hexarhenium(III) clusters, [Re6(mu3-S)8X6]4- (X = Cl-, Br-, and I-), in the crystalline phase were studied in detail. An increase in T from 30 to 70 K resulted in a red-shift of the emission spectrum of the cluster, while an increase in T above 70 K gave rise to a gradual blue-shift of the spectrum. On the other hand, the emission lifetime of the cluster decreased sharply from 30-40 to 13-20 micros on going from 30 to 60 K, while that decreased gradually above 60 K: 5-6 micros at 290 K. Such emission behaviors of [Re6(mu3-S)8X6]4- were observed irrespective of X. The results were then analyzed by assuming the contributions of the emissions from the lowest-energy excited triplet-state sublevels. The present study demonstrated that the characteristic T dependent emission spectra and lifetimes of [Re6(mu3-S)8X6]4- were explained reasonably by a single context of the contributions of the emissions from four excited triplet-state sublevels.

Journal Article↗

Early clinical results of St. Jude Medical Symmetry aortic connector.

An automated anastomosis device named St. Jude Medical symmetry aortic connector has been used worldwide for off-pump coronary artery bypass grafting. However, early graft obstruction was recently reported, and its predictors should be clarified. From April 2002 to March 2004, 38 patients in our institution underwent off-pump coronary artery bypass grafting using the St. Jude Medical Symmetry aortic connector for saphenous vein graft (SVG) procedures; measurement of intraoperative graft flow and postoperative coronary angiography was performed. Early SVG events occurred in 9 (24%) patients: 8 occlusion cases and 1 case of stenosis. Predictors of early SVG events were assessed from a comparative study. Univariate logistic regression identified hyperlipidemia as the only significant predictor of early SVG events (P = 0.02, odds ratio 7.78). Lower SVG flow rate and poor ejection fraction did not show statistical significance (P = 0.09, odds ratio 1.09 and P = 0.09, odds ratio 0.96). The SVG event rate was much higher for the left circumflex branch compared with other locations (31% vs. 9%, P = 0.03) and decreased with increasing aortic connector size (small, 32%; median, 14%; large, 0%). Multivariate analysis did not identify a predictor of SVG events. The aortic connector is associated with a high incidence of early SVG events. Patients should be cautiously selected and the procedure should not be used for left anterior descending coronary artery or culprit lesions.

Aged↗

Primary lung adenocarcinoma with heterotopic bone formation.

A 46-year-old man was referred to our hospital for the treatment of lung cancer. Computed tomography showed a well-defined tumor mass that was 50x45 mm in size and contained a trabecular pattern of calcification. Since he was diagnosed as having a primary lung adenocarcinoma (clinical stage IB), a left upper lobectomy with mediastinal lymph node dissection was performed. Histologically, the tumor was a poorly differentiated adenocarcinoma with rich fibrous stroma, in which there were island-shaped bone formation lesions. An immunohistochemical examination showed the expression of bone morphogenic protein-2 within tumor cells, which induce and stimulate bone formation. This finding may elucidate a possible mechanism of heterotopic bone formation.

Adenocarcinoma↗

Thoracic aneurysm rupture due to graft perforation after endovascular stent-grafting via median sternotomy.

We performed emergency repeat surgery for aneurismal rupture due to graft perforation with mechanical stress of the Z stent in a kinking graft after frozen elephant trunk procedure. Graft kinking occurred due to cranial migration of the Z stent. It is important to prevent stent dislodgement in order to achieve long-term durability and reliability in the frozen elephant trunk procedure.

Aged↗

Arch-first technique performed under hypothermic circulatory arrest with retrograde cerebral perfusion improves neurological outcomes for total arch replacement.

OBJECTIVE: From 1998, we have adopted the arch first technique (reconstruction of arch vessels first and distal anastomosis second) instead of the distal anastomosis first technique for total arch replacement. The aim is to reduce the period of deep hypothermic circulatory arrest and the retrograde cerebral perfusion time. We evaluate the surgical results of the arch first technique. METHODS: The arch first technique was used in 50 cases (38 male and 12 female), of average age 68 years, from 1998 to 2003. There were 33 true aneurysms and 10 chronic and seven acute type A dissections. Clinical results were evaluated and compared with the distal first technique used in 24 cases operated on between 1992 and 1998. These were 14 males and 10 females, with an average age of 68 years. There were 16 true aneurysms, and three chronic and five acute aortic dissections. RESULTS: For the arch first technique there is a significantly shorter circulatory arrest time (32 vs. 72min, P<0.0001), but similar body ischemic times (76 vs. 72min, N.S.). With the arch first technique, all but two patients awoke within 24h, with an average delay of 9.3h. In the distal first technique, two patients did not awaken and three patients showed delayed awakening, with an average awakening time of 24h. The arch first technique led to one hospital death (2%), due to residual aneurysm rupture. Reversible ischemic neurological deficit (RIND) was complicated in three cases (6%), but no stroke occurred during operation. In the distal first technique there were four strokes, one RIND and three hospital deaths (12.5%). The arch first technique gave a significantly lower intra-operative stroke rate (P=0.0030) and smaller hospital mortality (P=0.0615). The arch first technique led to five late deaths, with an 84.5% 3 year survival rate, and the distal first technique led to six late deaths with a 59.1% 3-year survival rate. CONCLUSIONS: The arch first technique is clearly superior to the conventional distal first technique in surgical mortality and morbidity regarding neurological outcome, and provides a higher survival rate and better quality of life. The arch first technique is an excellent method for total arch replacement.

Adult↗

Pressure-volume relationship in isolated working heart with crystalloid perfusate in swine and imaging the valve motion.

OBJECTIVE: It is widely accepted that both valve and cardiac functions are closely correlated. In order to investigate the relationship between the valve and cardiac functions, we developed a model of an isolated working heart with crystalloid perfusate in swine. We investigated the feasibility of this model to evaluate the precise left ventricular function using the pressure-volume relationship and metabolic measurement. Another objective was as a trial for the imaging and analysis of valvular interventions with a high-speed digital camera on this model. METHODS: Six isolated working hearts were subjected in the pressure-volume study, and additional three hearts were used in the valve imaging study. Measurement of the pressure-volume relationship was undertaken in situ before the heart was removed, and on the working heart mode during the initial 30 min as the baseline, and at every 60 min. Lactate levels were measured at every stage in the working heart mode. Mitral valve interventions were performed in three hearts, and valve motions were observed by a high-speed digital camera via the left ventricle. RESULTS: The end-systolic elastance maintained a baseline level (5.17+/-2.25) until 180 min and decreased at 240 min (3.97+/-1.97, NS) and 300 min (2.85+/-1.29, P<0.01) of the working heart mode as compared with baseline. The Tau maintained a constant level until 180 min and increased at 240 min (62.2+/-13.3, NS) and 300 min (85.5+/-43.4, P<0.05) as compared with baseline (50.3+/-13.6). The slope of the end-diastolic pressure-volume relationship gradually increased with no significance until 180 min and increased significantly (0.147+/-0.066, P<0.01 vs 0.067+/-0.041 at baseline). Lactate increased accumulatively. The total heart energy was reduced from the initial phase of the working heart mode. The valves were well captured by the high-speed digital camera. CONCLUSIONS: The systolic and diastolic functions of an isolated heart were preserved at an acceptable level for 180 min. The practical reliability of the swine working heart model was demonstrated. This model will be used reliably for the investigation of the interaction of valve and cardiac functions.

Animals↗

Late regression of left internal thoracic artery graft stenosis at the anastomotic site without intervention therapy.

OBJECTIVE: Intervention therapy has been recently performed on the left internal thoracic artery graft stenosis. The purpose of this study was to evaluate the natural course of the left internal thoracic artery graft stenosis at the anastomotic site and clarify whether intervention therapy should be performed early after surgery. METHODS: We investigated early angiographic results of the left internal thoracic artery graft in 343 consecutive patients who underwent coronary bypass surgery. In 100 of 343 patients who underwent follow-up angiography, the graft diameter and percentage diameter stenosis at the anastomotic site were compared between early postoperative and follow-up angiography. None of these patients underwent intervention therapy on the left internal thoracic artery graft. RESULTS: Of 343 patients, 46 showed 50% or greater diameter stenosis, and 20 showed 70% or greater diameter stenosis at the anastomotic site. In the 100 patients with follow-up angiography, the graft diameter significantly increased (1.8 +/- 0.4 vs 2.1 +/- 0.5 mm, P < .0001) at follow-up angiography. The percentage diameter stenosis significantly decreased (69% +/- 13% vs 35% +/- 20%, P < .0001) at follow-up angiography in the patients with 50% or greater diameter stenosis at early postoperative angiography. Regression of left internal thoracic artery graft stenosis was detected in most patients with 70% or greater diameter stenosis. CONCLUSIONS: Our study demonstrated that left internal thoracic artery graft stenosis at the anastomotic site at early postoperative angiography might improve without intervention therapy. We should consider the natural course of the left internal thoracic artery graft stenosis in determining the indication of intervention therapy early after surgery.

Adult↗

Subtype switching of L-Type Ca 2+ channel from Cav1.3 to Cav1.2 in embryonic murine ventricle.

BACKGROUND: Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS: Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was higher than that of Cav1.2 mRNA. With development, Cav1.2 mRNA increased and Cav1.3 mRNA decreased. Analysis of Cav1.3 splicing variants showed that Cav1.3(1b) mRNA was expressed at a higher density than Cav1.3(1a) mRNA. Cav1.3 protein was detected only at 9.5 dpc, whereas Cav1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca2+ currents were prominent at 9.5 dpc. The Ca2+ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca2+ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca2+ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. CONCLUSIONS: The Cav1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity.

Animals↗

Natural history of a dilated ascending aorta after aortic valve replacement.

BACKGROUND: Little information is available regarding the incidence of aortic dissection or rupture in patients with a dilated ascending aorta after aortic valve replacement (AVR). The present clinical study aimed to demonstrate the incidence of aortic complications after AVR in patients with a dilated ascending aorta and to clarify those risk factors associated with the progression of a dilated ascending aorta or late aortic events. METHODS AND RESULTS: A total of 35 patients with a dilated ascending aorta at the time of AVR were enrolled. A dilated ascending aorta was defined as 40 mm or greater in diameter by preoperative computed tomography or operative findings. The baseline ascending aorta diameter ranged from 40 to 55 mm with a mean of 44.8+/-4.4 mm. There was a high frequency of bicuspid valve disease in patients with a dilated ascending aorta (57%). The mean follow-up interval was 8.1+/-3.5 years (range: 2.3-13). Aortic events occurred in 5 patients (aortic dissection in 1, rupture in 2, reoperation in 2) during the follow-up. One aortic dissection developed at a baseline aortic size of 42 mm, whereas 2 aortic ruptures occurred at baseline aortic sizes of 47 mm and 50 mm. There was no statistically significant univariate association between any of the patient clinical characteristics and late aortic events or ascending aortic progression. CONCLUSION: Although the clinical course of patients with a dilated ascending aorta is unpredictable, aortic events may occur even in patients with a baseline aortic diameter of <50 mm. Therefore, preventive aortic surgery at the time of AVR should be considered to prevent aortic dissection or rupture in patients with an even slightly dilated ascending aorta with a diameter of 40 to 50 mm, unless the patient has a high operative risk or older age.

Adolescent↗

Viral diarrhea in Japanese children: results from a one-year epidemiologic study.

A total of 557 fecal specimens from infants and children with acute gastroenteritis in five places (Maizuru, Tokyo, Sapporo, Saga and Osaka) in Japan from July 2002 to June 2003 were tested for the presence of diarrheal viruses by RT-PCR, PRHA, RNA-PAGE and latex agglutination methods. Of these, 56.4% (314) were found positive for diarrheal viruses. Among them, group A rotavirus was the most prevalent (43.6%, 137 of 314) followed by norovirus (29.9%, 94 of 314), adenovirus (7.6%, 24 of 314), group C rotavirus (6.4%, 20 of 314), sapovirus (5.1%, 16 of 314) and astrovirus (1.6%, 5 of 314), respectively. A high rate (7.4%, 19 of 314) of viral mixed infections, including one triple infection (adenovirus, norovirus and astrovirus) was demonstrated. Norovirus infection that usually has a peak during November and January in Japan was detected year-round and highest in September in our study. Norovirus was subjected to molecular genetic analysis by sequencing. The results clearly indicated that norovirus group II was a dominant genogroup (94.3%, 100 of 106). It is noteworthy that noroviruses detected in this study were classified into 8 genotypes (GI/1, GI/4, GII/2, GII/3, GII/4, GII/5, GII/6 and GII/12). Of these, NVGII/4 was the predominant genotype, followed by NVGII/6, and these presented 75.6% (80 of 106) and 11.3% (12 of 106), respectively. Another interesting feature in our study was the sudden appearance and disappearance of SaitamaU16-like strains belonging to NVGII/6 in the short period (January 2003 to June 2003). Our findings confirmed the presence of many diarrheal viruses co-circulating among Japanese infants and children and showed the great genetic diversity among norovirus.

Acute Disease↗

Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer.

Non-small cell lung cancer frequently shows loss of heterozygosity of the chromosome 3p21.3 region and several genes such as RASSF1A, BLU, and SEMA3B have been identified as candidate tumor suppressor genes at this region since their downregulation and hypermethylation at their promoter regions were frequently detected in lung cancer. To determine whether these three genes are simultaneously inactivated during lung cancer development, we studied 138 primary non-small cell lung cancers for the promoter methylation status of these genes and allelic loss of the chromosome 3p21.3 region. We found promoter hypermethylation at 32% in RASSF1A, 30% in BLU, and 47% in SEMA3B. Allelic loss of 3p21.3 was detected in 54 (58%) of 93 informative tumors. Despite the weak association of methylation status among these three genes, there was no correlation between the methylation status of each gene and loss of heterozygosity. We also studied possible genes downstream of RASSF1A in 16 primary non-small cell lung cancers and found that the expressions of SM22 and SPARC were significantly downregulated in RASSF1A-hypermethylated tumors. Our results showed that, while candidate tumor suppressor genes at this locus can be simultaneously inactivated by epigenetic alterations, loss of heterozygosity without any hypermethylation of the three genes can also occur in some cases, suggesting that just one allelic loss might also be sufficient for the inactivation of any of these genes for lung cancer development.

Aged↗

Time-resolved total internal reflection fluorescence study on hybridization of complementary single-stranded DNAs at a water/oil interface.

Hybridization of complementary single-stranded DNAs (ssDNA) at a water/CCl4 interface was studied on the basis of picosecond total internal reflection fluorescence spectroscopy. Complementary ssDNAs dissolved in water were shown to produce the relevant double-stranded DNA (dsDNA) at a water/CCl4 interface in the presence of octadecylamine (ODA) in the oil phase, while hybridization between ssDNAs did not proceed in the water phase, as demonstrated by the fluorescence dynamics of ethidium bromide as a probe for the DNA structure. The structures of dsDNA and the roles of ODA in hybridization of ssDNA at the interface were discussed.

Amines↗

p53 apoptotic pathway molecules are frequently and simultaneously altered in nonsmall cell lung carcinoma.

BACKGROUND: Lung carcinomas show frequent inactivation of the p53 tumor suppressor, which regulates an apoptotic pathway. The objective of the current study was to assess how the p53 apoptotic pathway is altered in nonsmall cell lung carcinoma (NSCLC), especially in tumors without p53 alterations. METHODS: p53, its upstream regulators (p14(ARF) and HDM2), and downstream effectors of the apoptotic pathway (BAX and BCL2) were studied in 118 NSCLC specimens. p53 was analyzed by single-stranded conformation polymorphism analysis covering exons 2-11 and by immunohistochemistry (IHC). p14(ARF) was analyzed by methylation-specific polymerase chain reaction and IHC. HDM2 was analyzed using Southern blot analysis and IHC. BAX and BCL2 were analyzed by IHC. Two other upstream regulators that regulate the stability of HDM2, PTEN and HAUSP, also were studied. RESULTS: Of 118 NSCLC specimens that were analyzed, p53 alterations were detected in 74 tumors (63%), p14(ARF) inactivation was detected in 53 tumors (45%), and overexpression of HDM2 was found in 31 tumors (26%), including 6 tumors with gene amplification. Although p53 inactivation and HDM2 overexpression were detected simultaneously, HDM2 gene amplification was observed only in tumor specimens without p53 mutations. IHC revealed PTEN down-regulation in 22 of 88 tumors (25%). HAUSP Northern blot analysis demonstrated several-fold differences in gene expression that did not correlate with p53 alterations. Of 118 NSCLC specimens, expression of BAX and BCL2 expression were detected in 46 tumors (39%) and 17 tumors (14%), respectively. Finally, ASPP1 and ASPP2, molecules involved in mediating the transcription function of p53, were not found to be aberrantly expressed when tested by Northern blot analysis. CONCLUSIONS: Overall, two or more p53 pathway components were found to be frequently altered in patients with NSCLC. Greater than 90% of the alterations were due to abnormalities of p53, p14(ARF), or HDM2. Therefore, the inactivation of one or more components of the p53 pathway appears to be a prerequisite for the development of most NSCLCs.

Adult↗

Real time 3-D echocardiography in cardiac surgery.

OBJECTIVE: Real time 3-D echocardiography provides real time live images of intracardiac anatomy. We evaluate its clinical application for intraoperative echocardiography. METHOD: The "xStream"3-D architecture designed with "xMatrix array" using approximately 3,000 transducer elements achieves live digital volume imaging in real time 3-D echocardiography (SONOS 7500, Philips Medical Systems, Inc.). Intraoperative echocardiography was performed in mitral (n = 14) and aortic valve diseases (n = 6), 4 heart anomaly, 4 aortic diseases and 15 normal anatomies. RESULTS: Heart valves were depicted via enface view. Simultaneous movement of leaflets and subvalvular apparatus can be observed. Prolapsed leaflets are easily detected and regurgitated jets are detected as 3-D color images. The four cardiac chambers were observed in their real shape and size. Septum defects were also depicted in real shape, size and position. Precise intracardiac anatomy was observed in cardiac anomalies. Information on the endothelium, intimal flap, entry, reentry and aortic wall character was provided and allowed for planning in aortic surgery. CONCLUSION: Live 3-D echocardiography provides excellent depiction of any cardiac and aortic anatomy in any direction and greatly enhances efficiencies in planning appropriate surgical procedures.

Cardiac Surgical Procedures↗

Convenient training method for aortic cannulation: glove- and-peel method.

Aortic cannulation is a difficult technique for young cardiovascular surgeons. A convenient training method for this procedure is introduced in this paper. After two gloves are worn on a hand, they are removed together, then a piece of mandarin-orange peel is inserted between the gloves. The inner glove is filled with water and the mouth of the inflated gloves is securely tied with a strong ligature. Then this "glove balloon" is set inside a container to stabilize it. Purse-string stitches are placed on the orange peel. After the center of the purse string is incised with a number 11 blade, a cannula is introduced. This "glove-and-peel method" will help young cardiovascular surgeons to become accustomed to aortic cannulation.

Aorta↗

Beating mitral valve replacement for a patient with porcelain aorta.

Beating mitral valve replacement was performed for mitral valve stenosis in a patient with a porcelain aorta after aortic valve replacement. The 77-year-old patient had developed heart failure several times. A chest computed tomographic scan revealed severe calcification on the ascending aorta and aortic arch. A cardiopulmonary bypass was established by bicaval drainage and aortic return after epiaortic echographic evaluation of the ascending aorta. The mitral valve was successfully replaced under a beating heart.

Aged↗

Mid-term structural change in the radial artery grafts after coronary artery bypass grafting.

BACKGROUND: Currently, excellent patency rates of radial artery grafts for coronary artery bypass grafting in the early period have been reported. However, the long-term result of radial artery grafts remains unclear. We investigated the midterm structural change in radial artery grafts using intravascular ultrasound imaging (IVUS). METHODS: IVUS studies were performed on 15 radial artery grafts in the early phase and 11 in the midterm phase (20.3 +/- 13.7 days and 37.6 +/- 7.2 months after surgery, respectively). The radial artery grafts were observed throughout the entire length and 10 cross-sectional images were selected from each graft for measurement of the thickness of the intima (IN) and intima-plus-media (IN + MD). Grafts having palpable arteriosclerosis at the time of harvesting were excluded. IN and IN + MD were compared between the early and midterm phases using repeated measures analysis of variance. The coefficient of variation of IN and IN + MD was calculated as an index of irregularity and compared between the phases. RESULTS: IVUS revealed uniform and thin intima and media in the early and midterm groups and IVUS images were similar between the groups. There was no significant difference in both IN and IN + MD between the groups (IN, p = 0.83; IN + MD, p = 0.55). The median of coefficient of variation of IN and IN + MD was 8.5% and 8.1% in the early group and 8.7% and 9.3% in the midterm group. Again, there was no significant difference between the groups (IN, p = 0.87; IN + MD, p = 0.27). CONCLUSIONS: The present study suggested that structural changes rarely developed in radial artery grafts over several years after surgery.

Coronary Artery Bypass↗