Management of ostium secundum atrial septal defect in the era of percutaneous trans-catheter device closure: 7-Year experience at a single institution

AbstractObjectivesThis study aimed to review the single institutional experience of the repair of secundum atrial septal defect (ASD) after the initiation of percutaneous trans-catheter device closure, to confirm the current management strategy and outcomes.MethodsFrom August 2005 to December 2012, a total of 1026 (659 females, age 27±21 years) consecutive patients underwent the repair of ASD. Including eight patients who converted to surgical repair, 317 patients (31%) underwent surgical repair and 709 (69%) underwent trans-catheter device closure.ResultsAn embolized device into the left atrium was surgically retrieved in one patient soon after trans-catheter device closure without any postoperative complications. The other patient developed left atrium to aorta fistula due to late erosion, and required the removal of implanted device and patch closure of fistula and ASD 3 months after trans-catheter device closure. Whereas serious central nerve system complications occurred in three patients after the surgical repair including a 75-year-old patient with postoperative transient atrial fibrillation who subsequently developed aspiration pneumonia and died; there were no mortalities and no morbidities associated with cranial nerve function after trans-catheter device closure. A number of patients approached through partial sternotomy with limited skin incision have increased per year, and the length of skin incision was 5.1±1.2cm in pediatric patients weighing less than 15kg (n=40), 6.9±1.9cm in the remaining pediatric patients (n=91), and 10.0±2.5cm in young adult females (n=10).ConclusionPercutaneous trans-catheter ASD closure was safely performed under the support of a surgical team. The cosmetic outcome of surgical closure is improving after initiation of partial sternotomy via limited skin incision for the pediatric population and young adult females. Prior to the treatment, the physicians must thoroughly inform patients and families of the advantages and disadvantages of both treatment options

Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression

As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and itspresence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cellsincrease with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV)were used for double-label immunofluorescence of 53BP1 and Ki-67/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern (P < .0001). There was a significant correlation between 53BP1 and p16INK4a expression levels(r ? .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes

Origins and Evolution of MicroRNA Genes in Plant Species

MicroRNAs (miRNAs) are among the most important regulatory elements of gene expression in animals and plants. However, their origin and evolutionary dynamics have not been studied systematically. In this paper, we identified putative miRNA genes in 11 plant species using the bioinformatic technique and examined their evolutionary changes. Our homology search indicated that no miRNA gene is currently shared between green algae and land plants. The number of miRNA genes has increased substantially in the land plant lineage, but after the divergence of eudicots and monocots, the number has changed in a lineage-specific manner. We found that miRNA genes have originated mainly by duplication of preexisting miRNA genes or protein-coding genes. Transposable elements also seem to have contributed to the generation of species-specific miRNA genes. The relative importance of these mechanisms in plants is quite different from that in Drosophila species, where the formation of hairpin structures in the genomes seems to be a major source of miRNA genes. This difference in the origin of miRNA genes between plants and Drosophila may be explained by the difference in the binding to target mRNAs between plants and animals. We also found that young miRNA genes are less conserved than old genes in plants as well as in Drosophila species. Yet, nearly half of the gene families in the ancestor of flowering plants have been lost in at least one species examined. This indicates that the repertoires of miRNA genes have changed more dynamically than previously thought during plant evolution

Evolutionary Changes of the Target Sites of Two MicroRNAs Encoded in the Hox Gene Cluster of Drosophila and Other Insect Species

MicroRNAs (miRs) are noncoding RNAs that regulate gene expression at the post-transcriptional level. In animals, the target sites of a miR are generally located in the 3′ untranslated regions (UTRs) of messenger RNAs. However, how the target sites change during evolution is largely unknown. MiR-iab-4 and miR-iab-4as are known to regulate the expression of two Hox genes, Abd-A and Ubx, in Drosophila melanogaster. We have therefore studied the evolutionary changes of these two miR genes and their target sites of the Hox genes in Drosophila, other insect species, and Daphnia. Our homology search identified a single copy of each miR gene located in the same genomic position of the Hox gene cluster in all species examined. The seed nucleotide sequence was also the same for all species. Searching for the target sites in all Hox genes, we found several target sites of miR-iab-4 and miR-iab-4as in Antp in addition to Abd-A and Ubx in most insect species examined. Our phylogenetic analysis of target sites in Abd-A, Ubx, and Antp showed that the old target sites, which existed before the divergence of the 12 Drosophila species, have been well maintained in most species under purifying selection. By contrast, new target sites, which were generated during Drosophila evolution, were often lost in some species and mostly located in unalignable regions of the 3′ UTRs. These results indicate that these regions can be a potential source of generating new target sites, which results in multiple target genes for each miR in animals

Origins and Evolution of MicroRNA Genes in Drosophila Species

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level. To obtain some insights into the origins and evolutionary patterns of miR genes, we have identified miR genes in the genomes of 12 Drosophila species by bioinformatics approaches and examined their evolutionary changes. The results showed that the extant and ancestral Drosophila species had more than 100 miR genes and frequent gains and losses of miR genes have occurred during evolution. Although many miR genes appear to have originated from random hairpin structures in intronic or intergenic regions, duplication of miR genes has also contributed to the generation of new miR genes. Estimating the rate of nucleotide substitution of miR genes, we have found that newly arisen miR genes have a substitution rate similar to that of synonymous nucleotide sites in protein-coding genes and evolve almost neutrally. This suggests that most new miR genes have not acquired any important function and would become inactive. By contrast, old miR genes show a substitution rate much lower than the synonymous rate. Moreover, paired and unpaired nucleotide sites of miR genes tend to remain unchanged during evolution. Therefore, once miR genes acquired their functions, they appear to have evolved very slowly, maintaining essentially the same structures for a long time

A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese-Americans, and US-Whites

[Aims] Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD). [Methods and results] We analysed a population-based sample of 1212 men, aged 40–49 years free of clinical cardiovascular disease recruited in 2002–06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA. [Conclusion] In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40–49 years regardless of the BMI level

高齢者のADL・QOLとその関連要因に関する日本人および日系米人比較国際共同研究

厚生労働科学研究費研究成果報告書研究種目: 厚生労働科学研究費補助金 長寿科学総合研究推進事業（国際共同研究事業）研究年度: 2008研究代表者: 上島 弘嗣（滋賀医科大学・医学部・教授）共同研究者: 三浦 克之（滋賀医科大学・医学部・准教授）共同研究者: 喜多 義邦（滋賀医科大学・医学部・講師）共同研究者: 村上 義孝（滋賀医科大学・医学部・准教授）共同研究者: 門脇 崇（滋賀医科大学・医学部・助教）共同研究者: 奥田 奈賀子（滋賀医科大学・医学部・特任助教）共同研究者: 高嶋 直敬（滋賀医科大学・医学部・特任助教）共同研究者: 門田 文（滋賀医科大学・医学部・博士課程）共同研究者: 藤吉 朗（滋賀医科大学・医学部・博士課程）共同研究者: 門脇 紗也佳（滋賀医科大学・医学部・特任助教

Smoking habits and progression of coronary and aortic artery calcification: A 5-year follow-up of community-dwelling Japanese men.

Background and aims: To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression.Methods: At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston\u27s method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry.Results: A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked.Conclusions: Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease