PubMed Health⌕ Search

Biomedical subjects

Yuichi Sato

Publications and source records attributed to Yuichi Sato.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

Regression of an atherosclerotic coronary artery plaque demonstrated by multislice spiral computed tomography in a patient with stable angina pectoris.

Multislice spiral computed tomography (MSCT) permits direct visualization of not only coronary artery stenosis but also atherosclerotic plaques in patients with coronary artery disease. In this report, we describe a patient with stable angina in whom the regression of the plaque was documented by serial MSCT examinations. In the patient, a 46-year-old man with stable angina, MSCT revealed a stenotic lesion at the proximal portion of the left anterior descending artery. Axial, curved multiplanar reconstruction and cross-sectional images consistently depicted a protruding computed tomography low-signal mass suggesting an atherosclerotic plaque. Intracoronary ultrasound (ICUS) also documented an eccentric soft plaque with an echo-lucent mass suggesting a lipid core. Lipid-lowering therapy with pravastatin was started. Follow-up MSCT performed 7 months later documented an increase in the luminal area while the external vessel area remained unchanged. The regression of the plaque was also confirmed by a follow-up ICUS study. MSCT was thought to be feasible for serial evaluation of the plaque size and texture.

Angina Pectoris↗

Cationic comb-type copolymers as an artificial nucleic acid-chaperone: spectroscopic analyses for DNA/copolymer interaction.

We have reported previously that the cationic comb-type copolymer, PLL-g-Dex, accelerated DNA strand exchange reaction while stabilizing DNA duplexes. In this research, we showed the effects of cationic PLL-g-Dex copolymer on hybridization of self-complementary octamer oligonucleotides. NMR studies suggested that PLL-g-Dex copolymer preferentially interacted with a duplex DNA rather than a single-stranded DNA, and did not perturb local structures of DNA duplexes. CD studies also supported inert nature of the copolymer upon hybrid structure. From these results we concluded that the accelerating mechanisms of the copolymer did not involved partial perturbation of duplex structure.

Biopolymers↗

Design of artificial nucleic acid chaperones for DNA engineering.

We have shown that the comb-type copolymer consisting of a polycation backbone and hydrophilic side chains stabilizes DNA hybrids. Furthermore, the copolymers showed the activity to accelerate DNA strand exchange reactions between double helical DNA and its complementary DNA. The copolymer was considered to stimulate breakage and reassociation of base pairing and act as an artificial nucleic acid chaperone. The polymer's chaperoning activity was elaborated for rapid and precise judging of a subtle difference in DNA sequences. One base alternation out of 20mer DNA was quickly detected by the strand exchange assay employing the copolymer. From these, we conclude that the copolymer would be a useful material in DNA engineering that employs rapid and precise DNA folding.

Biopolymers↗

Polycation-accelerated strand exchange (PASE) for SNPs typing.

In the previous study (Chem. Eur. J., 7, 176 (2001), J. Am. Chem. Soc., 124, 12676 (2002)), we demonstrated that the cationic comb-type copolymer (PLL-g-Dex, CCC) composed of a cationic poly(L-lysine) backbone and water-soluble side chains of dextran accelerated the DNA strand exchange reaction between double helical DNA and its homologous single strand. In this study, Polycation-Accelerated Strand Exchange (PASE) assay was applied to discriminate single-base mismatch in DNA sequence such as single nucleotide polymorphisms (SNPs). We could discriminate the 20mer DNA with a single-base mismatch from the full matched DNA with high efficacy by PASE.

Base Pair Mismatch↗

A novel murine model of oral candidiasis with local symptoms characteristic of oral thrush.

A conventional and easy method to establish a murine oral candidiasis model, which has not only a stable yeast population in the oral cavity but also symptoms characteristic of oral thrush, was developed by using a sedative agent. Mice were immunosuppressed with prednisolone and were given tetracycline hydrochloride. They were orally infected with 10(6) viable cells of Candida albicans by means of a cotton swab and enough chlorpromazine chloride had been injected to keep them in a sedative state about for 3 hr after inoculation. From day 3 to day 7 post inoculation, 10(5)-10(6) colony forming units of Candida were recovered from the oral cavity of each mouse and whitish, curd-like patches were observed on most parts of tongue. Microscopically, germ tubes had appeared on the tongue surface. This model would be a useful experimental oral candidiasis for investigating the pathogenesis of C. albicans oral infection and the efficacy of various antifungal agents microbiologically and symptomatically.

Amphotericin B↗

Noninvasive coronary artery imaging by multislice spiral computed tomography.

Although the excellent spatial resolution of multislice spiral computed tomography (MSCT) enables the coronary arteries to be visualized, its limited temporal resolution results in poor image reproducibility because of cardiac motion artifact (CMA) and hence limits its widespread clinical use. A novel retrospectively ECG-gated reconstruction method has been developed to minimize CMA. In 88 consecutive patients, the scan data were reconstructed using 2 retrospectively ECG-gated reconstruction methods. Method 1: the end of the reconstruction window (250 ms) was positioned at the peak of the P wave on ECG, which corresponded to the end of the slow filling phase during diastole immediately before atrial contraction. Method 2 (conventional method): relative retrospective gating with 50% referred to the R-R interval was performed so that the beginning of the reconstruction window (250 ms) was positioned at the halfway point between the R-R intervals of the heart cycle. The quality of the coronary artery images was evaluated according to the presence or absence of CMA. The assessment was applied to the left main coronary artery (LMCA), the left anterior descending artery (LAD, segments #6, #7 and #8), the left circumflex artery (LCx, segments #11 and #13) and the right coronary artery (RCA, segments #1, #2 and #3). The first diagonal artery (#9-1), the obtuse marginal artery (#12-1), the posterior descending artery (#4-PD), the atrioventricular node branch (#4-AV) and the first right ventricular branch (RV) were also evaluated. Of the 88 patients, 85 were eligible for image evaluation. Method 1 allowed visualization of the major coronary arteries without CMA in the majority of patients. The LCA system (segments #5-7, #11 and #13) and the proximal portion of the RCA were visualized in more than 94% of patients. Artifact-free visualization of the distal portion of the LAD (segment #8) and RCA (#4PD and #4AV), and side branches (#9-1, #12-1 and RV) was also achieved in more than 80% of patients. On the other hand, CMA occurred frequently on images obtained by Method 2. The LCx and RCA systems were the most affected by CMA, revealing only 41% artifact-free visualization of the segment #13, 39% of #1, 15% of #2 and 32% of #3. Thus, Method 1, which avoids the ventricular motion occurring during the rapid filling and atrial contraction phases, gives superior image quality over the conventional ECG-gated reconstruction method.

Algorithms↗

Noninvasive assessment of coronary artery disease by multislice spiral computed tomography using a new retrospectively ECG-gated image reconstruction technique.

The present study was designed to investigate the accuracy of multislice spiral computed tomography (MSCT) in detecting coronary artery disease, compared with coronary angiography (CAG), using a new retrospectively ECG-gated reconstruction method that reduced cardiac motion artifact. The study group comprised 54 consecutive patients undergoing MSCT and CAG. MSCT was performed using a SOMATOM Volume Zoom (4-detector-row, Siemens, Germany) with slice thickness 1.0 mm, pitch 1.5 (table feed: 1.5 mm per rotation) and gantry rotation time 500 ms. Metoprolol (20-60 mg) was administered orally prior to MSCT imaging. ECG-gated image reconstruction was performed with the reconstruction window (250 ms) positioned immediately before atrial contraction in order to reduce the cardiac motion artifact caused by the abrupt diastolic ventricular movement occurring during the rapid filling and atrial contraction periods. Following inspection of the volume rendering images, multiplanar reconstruction images and axial images of the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx) and right coronary artery (RCA) were obtained and evaluated for luminal narrowing. The results were compared with those obtained by CAG. Of 216 coronary arteries, 206 (95.4%) were assessable; 10 arteries were excluded from the analysis because of severe calcification (n=4), stents (n=3) or insufficient contrast enhancement (n=3). The sensitivity to detect coronary stenoses >or=50% was 93.5% and the specificity to define luminal narrowing <50% was 97.2%. The positive predictive value and the negative predictive value were 93.5% and 97.2%, respectively. The sensitivity was still satisfactory (80.6%) even when non-assessable arteries were included in the analysis. The new retrospectively ECG-gated reconstruction method for MSCT has excellent diagnostic accuracy in detecting significant coronary artery stenoses.

Angina Pectoris↗