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Biomedical subjects

Yuichi Sato

Publications and source records attributed to Yuichi Sato.

At least 73 records · Page 4Linked to original sources

Incremental value of regional wall motion analysis immediately after exercise for the detection of single-vessel coronary artery disease: study by separate acquisition, dual-isotope ECG-gated single-photon emission computed tomography.

BACKGROUND: Although the detection of wall motion abnormalities gives incremental value to myocardial perfusion single-photon emission computed tomography (SPECT) in the diagnosis of extensive coronary artery disease (CAD) and high-grade single-vessel CAD, whether or not it is useful in the diagnosis of mild, single-vessel CAD has not been studied previously. METHODS AND RESULTS: Separate acquisition, dual isotope ECG-gated SPECT was performed in 97 patients with a low likelihood of CAD (Group 1) and 46 patients with single-vessel CAD (Group 2). Mild CAD was defined by stenosis of 50-75% (Group 2a, n=22) and moderate to severe CAD was defined by stenosis >/=76% (Group 2b, n=24). Myocardial perfusion and wall motion were graded by a 5 point-scale, 20-segment model. The sensitivity of myocardial perfusion alone was 50% for Group 2a, 83% for Group 2b and 67% for Group 2 as a whole. The overall specificity was 90%. When the wall motion analysis was combined, the sensitivity was increased to 82% in Group 2a and 92% in Group 2b. CONCLUSION: The ability to detect a wall motion abnormality immediately after exercise gives incremental diagnostic value to myocardial perfusion SPECT in the identification of mild, single-vessel CAD.

Aged↗

Detection of anomalous origins of the coronary artery by means of multislice computed tomography.

BACKGROUND: Anomalous origins of the coronary artery are rare, but may cause myocardial ischemia and sudden death. Thus, their reliable identification is crucial for any imaging method that attempts coronary artery visualization and of those available multislice computed tomography (MSCT), which provides excellent spatial resolution, may be the most promising. METHODS AND RESULTS: In consecutive 1,153 patients, MSCT identified 5 patients (0.43 %) with an anomalous origin of the coronary artery. The left circumflex artery (LCX) originated from the right sinus of Valsalva in 1 patient, and the right coronary artery originated from the left sinus of Valsalva and coursed between the aortic root and the pulmonary artery in 3 patients. In 1 patient, MSCT identified the absence of the LCX and high-grade atherosclerotic stenosis in the right coronary artery. CONCLUSION: MSCT can detect the anomalous origin and course of the coronary artery in relation to the great vessels. It is also useful for identifying atherosclerotic coronary artery disease superimposed on the anomalous vascular system.

Aged↗

Assessment of coronary artery abnormalities in a patient with Kawasaki disease by multislice computed tomography.

The high spatial resolution of multislice computed tomography (MSCT) permits direct visualization of the coronary artery system. In this report, we describe coronary artery abnormalities in a young adult with Kawasaki disease. MSCT detected a giant coronary artery aneurysm, coronary artery stenosis in the first diagonal artery, and a multi-layered structure in the right coronary artery and the left circumflex artery. These findings corresponded well to those obtained by coronary angiography. MSCT has the potential to be the standard diagnostic tool for the follow-up evaluation of coronary artery disease in adolescents and young adults with Kawasaki disease.

Adult↗

Specific enhanced expression of platelet-derived endothelial cell growth factor in submucosa of human colorectal cancer.

PURPOSE: Platelet-derived endothelial cell growth factor, identified to be an angiogenic factor, has been implicated in metastases of colorectal cancer. This study aimed to clarify the role and localization of platelet-derived endothelial cell growth factor associated with human colorectal cancer invasion. METHODS: Thirty-two patients with colorectal cancer who had undergone surgery were analyzed. Platelet-derived endothelial cell growth factor enzyme activities in the colorectal cancer specimens were measured. Cells that expressed platelet-derived endothelial cell growth factor were identified and localized by immunohistochemical analysis with anti-human platelet-derived endothelial cell growth factor antibody and by in situ hybridization with specific RNA probe. RESULTS: Platelet-derived endothelial cell growth factor enzyme activity increased significantly in cancer tissues compared with normal colonic mucosa at various distances from the cancer. Immunohistochemical analysis and in situ hybridization demonstrated platelet-derived endothelial cell growth factor expression in stromal macrophages and fibroblasts located in cancer tissues and surrounding noncancerous tissues, although the tumor cells and normal colonic mucosa were negative. The value of platelet-derived endothelial cell growth factor expression was highest at the border of the colorectal cancer (35.3 +/- 8.9 percent), followed by the cancer nest (15.2 +/- 9.2 percent) and normal mucosa (7.7 +/- 3.4 percent). In the border area, the highest value of platelet-derived endothelial cell growth factor expression was observed in the submucosa (35.3 +/- 8.9 percent), followed by the muscular propria (21.9 +/- 7.7 percent) and the subserosa (14.9 +/- 5.5 percent). CONCLUSIONS: Stromal macrophages and fibroblasts are responsible for elevated platelet-derived endothelial cell growth factor activity in colorectal cancer. The significance of enhanced expression of platelet-derived endothelial cell growth factor in the submucosa at the cancer border remains unclear. Cancer stroma may be an important factor for cancer angiogenesis and may serve as a treatment target through specific modulation of angiogenic factors.

Adult↗

Intermittent and recurrent hepatomegaly due to glycogen storage in a patient with type 1 diabetes: genetic analysis of the liver glycogen phosphorylase gene (PYGL).

We report a 19-year-old woman who had a history of type 1 diabetes with recurrent glycogen accumulation in the liver. During her infantile period she presented with no hepatomegaly nor growth retardation. On admission she was diagnosed with diabetic ketoacidosis (DKA). She also had hepatomegaly and elevated transaminase levels, but these abnormalities had resolved after administration of insulin. However, 4 weeks after DKA marked hepatomegaly and elevated transaminases were reappeared with simultaneous hypoglycemia which suggested an impaired glycogenolysis in the extraordinary conditions. We supposed the partial deficiency of liver glycogen phosphorylase activity in this patient and analyzed the liver glycogen phosphorylase gene (PYGL). Deduced amino acid sequence of the PYGL in this patient was completely identical to that reported by Burwinkel et al. (Y15233), however, the nucleotide sequence of PYGL cDNA was heterozygous for substitutions at positions Asp339 (GAT to GAC) on exon 9 and Ala703 (GCT to GCC on exon 17, respectively. These SNPs were also screened in 51 Japanese normal subjects by PCR-based direct sequencing or PCR-RFLP method. The same genotype observed in this patient was detected in 2 of 51(3.9%) normal subjects. These results suggest that the structure of PYGL coding sequence in this patient is unlikely to account for her excessive liver glycogen accumulation. Further studies including genetic analysis on the promoter region of the gene are necessary to clarify the etiology of susceptibility to excessive liver glycogen storage in patients with type 1 diabetes.

Adult↗

Synchronous evaluation of toxico- and pharmaco-dynamics of yttrium-90 by a novel autoradiographic procedure.

A synchronous evaluation was performed, using a quick in vivo [2-(14)C]thymidine labeling method, of the toxico- and pharmaco-dynamics of a given dose of yttrium-90 (90Y) at a given time after injection to nude BALB/c mice loaded with 10(7) HuO9 cells. Quantitative data were 14C-microautoradiographs of the liver lobule, intestinal crypts, epiphysial growth plate, secondary ossification center containing pluripotent stem cells, perifollicular zone containing unipotent stem cells in the spleen, and plasmacytoma cells in the osteogenic sarcoma in each mouse following a 10-min labeling with 14C at 0.5, 6, and 24 h after i.v. injection of 90Y. Results show that the cell proliferation rate of the stem cells in respective tissues was markedly suppressed, dependent on time after dosing and the dose of 90Y; 3.7, 37, 370, 3700, and 37,000 kBq per mouse (25 g). In addition to the above, the sensitivity of the proliferation rate was dependent on amitosis or mitosis and the AUC value of 90Y-concentration at specific locations of the cells in the mouse body. The most sensitive cells were the plasmacytoma cells, followed by the pluripotent and unipotent stem cells, the intestinal crypts, epiphysial growth plate, and liver cells.

Animals↗

hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors.

The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (P<0.0001, r=0.852), but was not related to neural cell adhesion molecule expression (P=0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P=0.041).

Adenocarcinoma↗

Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors.

A total of 111 pulmonary neuroendocrine tumors comprising 13 typical carcinoids, five atypical carcinoids, 44 large-cell neuroendocrine carcinomas and 49 small-cell carcinomas were immunohistochemically studied for dysregulated cyclin B1 expression and disruption of the Rb/p16/cyclin D1 pathway (Rb pathway), and the results were correlated with tumor proliferation activity and clinical outcome. Overexpression of cyclins B1 and D1, respectively, was detected in no and 15% typical carcinoids, 20 and 20% atypical carcinoids, 84 and 32% large-cell neuroendocrine carcinomas, 84 and 10% small-cell carcinomas. Loss of Rb and p16 expression, respectively, was observed in no and 14% typical carcinoids, no and 40% atypical carcinoids, 49 and 18% large-cell neuroendocrine carcinomas, 84 and 8% small-cell carcinomas. In summary, 29% typical carcinoids, 20% atypical carcinoids, 78% large-cell neuroendocrine carcinomas and 93% small-cell carcinomas had Rb pathway aberrations. Rb pathway aberration was mostly attributed to Rb loss in small-cell carcinomas, while p16 loss and/or cyclin D1 overexpression besides Rb loss also played an important role in large-cell neuroendocrine carcinomas, while cyclin D1 overexpression was the only cause of Rb pathway aberration in carcinoid tumors. Thus, both cyclin B1-associated G2/M arrest and Rb-mediated G1 arrest are consistently compromised in high-grade large-cell neuroendocrine carcinoma and small-cell carcinoma, but are generally intact or occasionally altered in carcinoid tumor; the mechanisms involved in Rb pathway aberration among the tumor categories are different, reflecting a genetic divergence among the individual tumor categories. Cyclin B1 expression closely correlated with the Ki-67 labeling index either in the individual tumor categories or overall tumors (P < 0.0001, r = 0.742), suggesting that cyclin B1 is one of the key factors regulating cell proliferation in pulmonary neuroendocrine tumors. Neither cyclins B1 and D1, Rb, p16, nor Ki-67 correlated with patient survival in individual tumor categories, suggesting that the prognostic significance of these factors is tumor-type specific.

Biomarkers, Tumor↗

Nucleation-synchronized strand displacement for highly sensitive DNA analysis.

Nucleation process is a rate-limiting step of DNA strand exchange reactions between double helical DNA and its complementary DNA. Here we designed the double stranded probes that have single stranded portion. The single stranded portion is responsible for the nucleation process and mismatch recognition. A single base mismatch in 25mer DNAs could be detected in a few minutes at ambient temperatures. Using this method, various types of SNPs are rapidly and reliably detected without any aids of enzymes or a special instrument.

Base Pair Mismatch↗

Evaluation of comb-type copolymers with different cationic groups as artificial nucleic acid chaperones.

We have demonstrated that cationic comb-type copolymers (CCCs) accelerate DNA hybridization and increase stability of DNA duplexes and triplexes. The CCCs were considered to act as nucleic acid chaperones that catalyze structural transitions of nucleic acid hybrids. In this study, CCCs with primary amino or guanidino groups were prepared to evaluate the effects of different cationic moieties upon the nucleic acid chaperoning activity. CCCs having guanidino groups have higher accelerating effect on DNA strand exchange reactions (SFRs) than that having primary amino groups. It was suggested that some modes of interactions, such as hydrogen bonding, other than ionic interactions between the copolymers and DNAs may be involved upon the strand exchange activation.

DNA↗

Preparation of cationic comb-type copolymer having guanidino moieties and its interaction with DNAs.

In order to evaluatet effects of different cationic moieties, such as primary amino and guanidino groups, on interactions between DNAs and cationic comb-type copolymers, comb-type copolymers having guanidino groups were prepared. The copolymers (GPLL-g-Dex) were obtained by guanidination of poly(L-lysine)-graft-dextran copolymers (PLL-g-Dex) using 1-guanyl-3,5-dimethylpyrazole nitrate under weak basic conditions. The resulting copolymers were characterized using NMR spectroscopy and size-exclusion chromatography-multiangle light scattering (SEC-MALS). The primary amino groups of the PLL backbones were thoroughly replaced with guanidino ones without any detectable side reactions, including fragmentation of PLL or Dex chains. The interactions of GPLL-g-Dex and PLL-g-Dex with DNAs were assessed by UV-melting curve measurements. These copolymers diversly affected the melting behavior of double-stranded DNA (dsDNA). GPLL-g-Dex has a lower ability to increase the Tm of dsDNA than PLL-g-Dex and also exhibits a higher affinity for dsDNA. The results suggest that the stability of dsDNA may be affected not only by ionic interaction between the copolymers and DNAs, but also by other modes of interactions, such as hydrogen-bondinginteractions.

Base Sequence↗

Evaluation of coronary artery remodeling in patients with acute coronary syndrome and stable angina by multislice computed tomography.

BACKGROUND: Multislice computed tomography (MSCT) was used to evaluate coronary artery remodeling in patients with acute coronary syndrome (ACS) and stable angina (SA). METHODS AND RESULTS: MSCT was performed in 31 patients with ACS and 26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling was assessed by the remodeling index (RI): RI >1.10 was defined as positive coronary artery remodeling (PCAR) and RI <0.95 was defined as negative coronary artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was present in 19 patients (61.3%) with ACS, but in none of the patients with SA (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was present in 18 patients (62.9%) with SA. The RI was significantly larger in patients with ACS (1.19+/-0.18) than in those with SA (0.89+/-0.10, p<0.0001). CONCLUSION: MSCT accurately assesses coronary artery remodeling.

Acute Disease↗

Evaluation of plaque texture by means of multislice computed tomography in patients with acute coronary syndrome and stable angina.

BACKGROUND: In the present study, multislice spiral computed tomography (MSCT), which allows non-invasive assessment of coronary artery plaque, was used to compare the CT density of plaque between patients with acute coronary syndrome (acs) and those with stable angina (sa). METHODS AND RESULTS: MSCT was performed in 20 patients with ACS (17 with acute myocardial infarction, 3 with unstable angina) and 22 patients with SA. The presence of the plaque was defined on the basis of multiplanar reformation and axial images. At least 4 regions of interest were then placed within the plaque and the minimum CT density was measured and expressed as Hounsfield units (HU). The number of plaques did not differ between the 2 groups, but the minimum CT density was significantly lower in patients with ACS (25+/-15 HU) than in those with SA (71+/-16 HU, range 46-101 HU, p<0.001). Similarly, the minimum plaque density was significantly lower in the culprit coronary segment (26+/-16 HU) than in the non-culprit segment (48+/-17 HU) in 15 ACS patients with multiple plaques. CONCLUSION: MSCT can potentially differentiate vulnerable from stable plaque in patients with coronary artery disease, although long-term, prospective analysis is needed to establish the conclusion.

Adult↗

Mismatch between results of myocardial fractional flow reserve (FFR) measurements and myocardial perfusion SPECT for identification of the severity of ischemia: pitfall of FFR in patients with prior myocardial infarction.

We experienced two rare cases of mismatch between the results of FFR and myocardial perfusion SPECT for identification of myocardial ischemia after myocardial infarction. If a FFR cutoff value of 0.75 is applied as in angina patients to patients with myocardial infarction, the severity of ischemia may be underestimated.

Aged↗

E, N-cadherins and beta-catenin expression in medulloblastoma and atypical teratoid/rhabdoid tumor.

Cadherins are cell-surface glycoproteins that mediate Ca2+-dependent, homophilic cell-cell adhesion. The classical cadherins, E- and N-cadherins, bind to beta-catenin, the lining protein. Dysfunctional expression of these factors seems to be related to tumor invasion and metastasis. This study examined the relationship between changes in E- and N-cadherins, and catenin expression, and biological behavior in medulloblastomas and atypical teratoid/rhabdoid tumors. Specimens of 13 medulloblastomas and two atypical teratoma/rhabdoid tumors were collected and stained immunohistochemically to detect E- and N-cadherins, and beta-catenin. None of the medulloblastomas were immunoreactive for E-cadherin, but both atypical teratoma/rhabdoid tumors were immunoreactive for E-cadherin at the cell-cell borders where epithelial differentiation occurred. In contrast, N-cadherin and beta-catenin were present at the cell-cell borders in 12 of the 13 medulloblastomas and both atypical teratoma/rhabdoid tumors. Nuclear beta-catenin staining was not present in the medulloblastomas or atypical teratoma/rhabdoid tumors. There was no significant difference in the Ki-67 staining index between patients with medulloblastomas showing high and low immunoreactivity for N-cadherin and beta-catenin. Moreover, immunoreactivity for N-cadherin and beta-catenin increased with dissemination in the medulloblastomas. Low immunoreactivity in medulloblastomas tended to be associated with a better prognosis. These results suggest that expression of E-cadherin is useful for the differential diagnosis of atypical teratoma/rhabdoid tumor and medulloblastoma, and the expression of N-cadherin or beta-catenin may be related to the biological behavior of medulloblastomas.

Cadherins↗

Cationic comb-type copolymers for DNA analysis.

Genetic diagnoses, such as single nucleotide polymorphism (SNP) typing, allow elucidation of gene-based physiological differences, such as susceptibility to diseases and response to drugs, among individuals. Many detection technologies, including allele-specific hybridization, allele-specific primer extension and oligonucleotide ligation, are being used to discriminate SNP alleles. These methods still have many unsolved practical issues. In general they require adequate and specific hybridizations of primer or probe DNAs with target DNAs. This frequently needs optimization of the probe/primer structures and operating conditions. In nature, highly homology-sensitive hybridization is assisted by a nucleic acid chaperone that reduces the energy barrier associated with breakage and reassociation of nucleic base pairs. Here we report a simple, quick, precise but enzyme-free method for SNP analysis. The method uses cationic comb-type copolymers (CCCs) producing high nucleic acid chaperone activities. A single-base mismatch in 20-mer DNA can be detected within a few minutes at ambient temperatures (25-37 degrees C). Even without careful optimization processes, the method has the sensitivity to detect the mismatches causing subtle changes (Delta T(m) equals approximately 1 degree C) in duplex thermal stability. CCCs may have various bioanalytical applications where precise hybridization of nucleic acids is needed.

Aryl Hydrocarbon Hydroxylases↗