A corrected transposition of the great arteries with situs inversus visceralis and cleft palate, but without other cardiac defects.

A 17-year-old female admitted for cleft palate surgery was referred for further evaluation of her cardiac condition. The patient had been diagnosed as dextrocardia at birth, without any cardiac murmurs. She has led a normal life. The apical impulse was felt at the fifth intercostal space at the right mid-clavicular line. The ECG and chest x-rays were strongly suggestive of corrected transposition of the great arteries (CTGA) with situs inversus visceralis. Findings of the two-dimensional and Dopplar echocardiograms showed CTGA with a mild morphologic tricuspid regurgitation without any other complicated cardiac anomalies. In the Japanese literature, 36 CTGA patients without associated cardiac defects have been reported. Of these, four patients revealed dextrocardia. To our knowledge, our patient is the first reported adult case without any cardiac defects, only minimal tricuspid regurgitation, situs inversus totalis and cleft palate.     

Plasma lipoprotein (a) levels in children with minimal lesion nephrotic syndrome

We studied the plasma lipoprotein (a)[Lp(a)] levels in 31 children with minimal lesion nephrotic syndrome (MLNS) in both stages of acute NS and remission.The mean Lp(a) levels in acute NS were significantly higher than those of the controls. The Lp(a) levels in remission were significantly lower than the Lp(a) levels in acute NS. In addition, the Lp(a) levels in remission were not significantly different from those of the controls. However, there were 5 patients whose Lp(a) levels remained higher than 30 mg/dl (the generally accepted limit for cardiovascular risk) after remission. Two of these 5 patients had Lp(a) levels greater than 40 mg/dl. In these patients apoprotein (a) [apo(a)] phenotypes were of lower molecular weight than those of the other 23 patients whose apo(a) phenotypes were examined. Additional episodes of relapse may put the patient with sustained elevated Lp(a) levels at significant risk for the development of cardiovascular disease in the long term. Received: 17 November 1998 / Revised: 9 March 1999 / Accepted: 16 March 1999     

Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats

Naunyn-Schmiedeberg's Archives of Pharmacology - In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in...     

Quantitative evaluation of the pulmonary microdistribution of TiO2 nanoparticles using X‐ray fluorescence microscopy after intratracheal administration with a microsprayer in rats

The unevenness of pulmonary nanoparticle (NP) distribution, which hinders the establishment of an absolute dose–response relationship, has been described as one of the limitations of intratracheal administration techniques for toxicological assessment of inhaled NPs. Quantification of the NP microdistribution would facilitate the establishment of a concentration–response relationship in localized regions of the lung; however, such quantitative methods have not been reported. Here, we established a quantitative method for evaluating pulmonary TiO₂ NP microdistribution in rats using X‐ray fluorescence microscopy. Ti intensity in lung sections from rats intratracheally administered 10 mg kg^–1 TiO₂ NPs with a microsprayer was measured using X‐ray fluorescence with a 100 µm beam size. Ti reference samples were prepared by dropping different concentrations of Ti solutions on glass slide or lung sections of untreated rat. Ti intensity increased linearly with Ti content in the reference samples on both substrates. The detection limit of TiO₂ was estimated to be 6.3 ng mm^–2. The reproducibility was confirmed for measurements done in the short‐ (2 weeks) and long‐term (6 months). The quantitative results of TiO₂ NP microdistribution suggested that more TiO₂ NPs were distributed in the right caudal and accessory lobes, which are located downstream of the administration direction of the NP suspension, and the lower portion of each lobe. The detection rates of TiO₂ NPs were 16.6–25.0%, 5.19–15.6%, 28.6–39.2%, 21.4–38.7% and 10.6–23.2% for lung sections from the right cranial, middle, caudal, accessory and left lobes, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer

Alterations of the HER-2 (erbB-2/neu) proto-oncogene have been associated with carcinogenesis and poor prognosis of certain cancers. A single nucleotide polymorphism (Ile/Val, A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. In our study, we examined the association between the HER-2 polymorphism and gastric carcinoma. The Ile/Ile, Ile/Val and Val/Val genotypes were found in 146 (68.9%), 56 (26.4%) and 10 (4.7%) of 212 gastric cancer patients and in 234 (81.5%), 48 (16.7%) and 5 (1.8%) of 287 control subjects, respectively. The Ile/Val or Val/Val genotype was significantly more frequent in patients than in controls (p = 0.005 and 0.033, respectively). The OR of Val/Val genotype then revealed a significantly enhanced risk of 3.25 (95% CI 1.09-9.70) compared to Ile/Ile genotype; heterozygous Ile/Val genotype showed an intermediate risk of 1.97 (1.27-3.06). In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p < 0.001). The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype. These results suggest that this nucleotide polymorphism in the transmembrane domain-coding region of HER-2 could be associated with development of gastric carcinoma and may serve as a predictor of risk for a malignant phenotype of gastric cancer. The association of HER-2 genotype with clinicopathologic characteristics of gastric cancer was also suggested, which has to be confirmed with a larger sample size.     

3-Amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the removal of both cyclobutane dimers and (6-4) photoproducts from the DNA of ultraviolet-irradiated E. coli

Heterocyclic amines have been isolated from cooked foods andfound to be mutagens and carcinogens. Among them, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2) were also found to enhance UV-induced mutation frequenciesin Escherichia coli at the concentrations where they were neithertoxic nor mutagenic by themselves. Using an immunological methodrecently developed to detect UV-induced DNA damage, we investigatedthe inhibitory effect of Trp-P-1 on the removal of both cyclobutanedimers and (6–4)photo-products from the DNA of UV-irradiatedE.coli. Cells repaired 60% of the initial cyclobutane dimerswithin 30 min and 75% at 120 min after UV-irradiation. Furthermore,the same cells repaired 90% of the initial (6–4)photoproductswithin 30 min. On the other hand, Trp-P-1 clearly showed inhibitionof repair of both photolesions in a concentration-dependentmanner. The levels of repair inhibition by Trp-P-1 were almostthe same between cyclobutane dimers and (6–4)photoproducts.These results suggested that the enhancing effect of Trp-P-1on UV-induced mutagenesis in E.coli stemmed from the inhibitionof the removal of photolesions from the DNA.     

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.