Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

Wilms' tumour is one of the most common solid tumours of childhood. 11p13 (WT1 locus) and 11p15.5 (WT2 locus) are known to have genetic or epigenetic aberrations in these tumours. In Wilms' tumours, mutation of the Wilms tumour 1 (WT1) gene at the WT1 locus has been reported, and the WT2 locus, comprising the two independent imprinted domains IGF2/H19 and KIP2/LIT1, can undergo maternal deletion or alterations associated with imprinting. Although these alterations have been identified in many studies, it is still not clear how frequently combined genetic and epigenetic alterations of these loci are involved in Wilms' tumours or how these alterations occur. To answer both questions, we performed genetic and epigenetic analyses of these loci, together with an additional gene, CTNNB1, in 35 sporadic Wilms' tumours. Loss of heterozygosity of 11p15.5 and loss of imprinting of IGF2 were the most frequent genetic (29%) and epigenetic (40%) alterations in Wilms' tumours, respectively. In total, 83% of the tumours had at least one alteration at 11p15.5 and/or 11p13. One-third of the tumours had alterations at multiple loci. Our results suggest that chromosome 11p is not only genetically but also epigenetically critical for the majority of Wilms' tumours

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

A non-catecholamine-producing sympathetic paraganglioma of the spermatic cord: the importance of performing candidate gene mutation analysis

textabstractBackground: Catecholamine-producing tumours are called pheochromocytomas when they are located in the adrenal gland and sympathetic paragangliomas when they are located elsewhere in the abdomen. Rarely these tumours do not produce catecholamines and even more rarely they arise in the spermatic cord. Over the past decade, systematic mutation analysis of apparently sporadic cases of pheochromocytomas and paragangliomas has elucidated the frequent presence of germ line mutations in one of five candidate genes, including RET, VHL, SDHB, SDHC, and SDHD. Clinical history and methods: We describe a 45-year-old man with a non catecholamine-producing paraganglioma of the spermatic cord. We performed SDHB immunohistochemistry and performed mutation analysis of the SDHB, SDHC, and SDHD genes. Results: There was no staining of tumour cells with SDHB immunohistochemistry, indicative of an SDH mutation. Mutation analysis demonstrated a germ line SDHD mutation (p.Val147Met). Conclusions: Systematic mutation analysis is required in paraganglioma patients for the detection of germ line mutations. This should be preceded by SDHB immunohistochemistry to limit the number of genes to be tested

A Systematic Review of Three-Dimensional Printing in Liver Disease

The purpose of this review is to analyse current literature related to the clinical applications of 3D printed models in liver disease. A search of the literature was conducted to source studies from databases with the aim of determining the applications and feasibility of 3D printed models in liver disease. 3D printed model accuracy and costs associated with 3D printing, the ability to replicate anatomical structures and delineate important characteristics of hepatic tumours, and the potential for 3D printed liver models to guide surgical planning are analysed. Nineteen studies met the selection criteria for inclusion in the analysis. Seventeen of them were case reports and two were original studies. Quantitative assessment measuring the accuracy of 3D printed liver models was analysed in five studies with mean difference between 3D printed models and original source images ranging from 0.2 to 20%. Fifteen studies provided qualitative assessment with results showing the usefulness of 3D printed models when used as clinical tools in preoperative planning, simulation of surgical or interventional procedures, medical education, and training. The cost and time associated with 3D printed liver model production was reported in 11 studies, with costs ranging from US$13 to US$2000, duration of production up to 100 h. This systematic review shows that 3D printed liver models demonstrate hepatic anatomy and tumours with high accuracy. The models can assist with preoperative planning and may be used in the simulation of surgical procedures for the treatment of malignant hepatic tumours

Host epigenetic modifications by oncogenic viruses

Epigenetic alterations represent an important step in the initiation and progression of most human cancers, but it is difficult to differentiate the early cancer causing alterations from later consequences. Oncogenic viruses can induce transformation via expression of only a small number of viral genes. Therefore, the mechanisms by which oncogenic viruses cause cancer may provide clues as to which epigenetic alterations are critical in early carcinogenesis

Safety of Postoperative Administration of Human Urinary Trypsin Inhibitor in Lung Cancer Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10(5), 6×10(5), and 9×10(5) units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.UMIN.ac.jp/ctr/UMIN000002410

IGF2 stimulates fetal growth in a sex- and organ-dependent manner

BackgroundInsulin-like growth factor 2 (IGF2) is a key determinant of fetal growth, and the altered expression of IGF2 is implicated in fetal growth disorders and maternal metabolic derangements including gestational diabetes. Here we studied how increased levels of IGF2 in late pregnancy affect fetal growth.MethodsWe employed a rat model of repeated intrafetal IGF2 administration in late pregnancy, i.e., during GD19-GD21, and measured the consequences on fetal organ weight and expression of insulin/IGF-axis components.ResultsIGF2 treatment tended to increase fetal weight, but only weight increase of the fetal stomach reached significance (+33±9%; P<0.01). Sex-dependent data analysis revealed a sexual dimorphism of IGF2 action. In male fetuses, IGF2 administration significantly increased fetal weight (+13±3%; P<0.05) and weight of fetal stomach (+42±10%; P<0.01), intestine (+26±5%; P<0.05), liver (+13±4%; P<0.05), and pancreas (+25±8%; P<0.05). Weights of heart, lungs, and kidneys were unchanged. In female fetuses, IGF2 increased only stomach weight (+26±9%; P<0.05). Furthermore, gene expression of insulin/IGF axis in the heart, lungs, liver, and stomach was more sensitive toward IGF2 treatment in male than in female fetuses.ConclusionData suggest that elevated circulating IGF2 in late pregnancy predominantly stimulates organ growth of the digestive system, and male fetuses are more susceptible toward the IGF2 effects than female fetuses.Fil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mazzucco, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gauster, Martin. Medizinische Universität Graz; AustriaFil: Desoye, Gernot. Medizinische Universität Graz; AustriaFil: Hiden, Ursula. Medizinische Universität Graz; Austri

Unmappable ventricular tachycardia after an old myocardial infarction. Long-term results of substrate modification in patients with an implantable cardioverter defibrillator

Purpose The frequent occurrence of ventricular tachycardia can create a serious problem in patients with an implantable cardioverter defibrillator. We assessed the long-term efficacy of catheter-based substrate modification using the voltage mapping technique of infarct-related ventricular tachycardia and recurrent device therapy. Methods The study population consisted of 27 consecutive patients (age 68 +/- 8 years, 25 men, mean left ventricular ejection fraction 31 +/- 9%) with an old myocardial infarction and multiple and/or hemodynamically not tolerated ventricular tachycardia necessitating repeated device therapy. A total of 31 substrate modification procedures were performed using the three-dimensional electroanatomical mapping system. Patients were followed up for a median of 23.5 (interquartile range 6.5-53.2) months before and 37.8 (interquartile range 11.7-71.8) months after ablation. Antiarrhythmic drugs were not changed after the procedure, and were stopped 6 to 9 months after the procedure in patients who did not show ventricular tachycardia recurrence. Results Median ventricular tachycardias were 1.6 (interquartile range 0.7-6.7) per month before and 0.2 (interquartile range 0.00-1.3) per month after ablation (P = 0.006). Nine ventricular fibrillation episodes were registered in seven patients before and two after ablation (P = 0.025). Median antitachycardia pacing decreased from 1.6 (interquartile range 0.01-5.5) per month before to 0.18 (interquartile range 0.00-1.6) per month after ablation (P = 0.069). Median number of shocks decreased from 0.19 (interquartile range 0.04-0.81) per month before to 0.00 (interquartile range 0.00-0.09) per month after ablation (P = 0.001). One patient had a transient ischemic attack during the procedure, and another developed pericarditis. Nine patients died during follow-up, eight patients due to heart failure and one patient during valve surgery. Conclusion Catheter-based substrate modification using voltage mapping results in a long-lasting reduction of cardioverter defibrillator therapy in patients with multiple and/or hemodynamically not tolerated infarct-related ventricular tachyarrhythmia

The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency

<p>Abstract</p> <p>Background</p> <p>Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and <it>TNFα </it>polymorphisms.</p> <p>Methods</p> <p>424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging <it>TNFα </it>were genotyped using TaqMan^®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.</p> <p>Results</p> <p>All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.</p> <p>Conclusion</p> <p>Variation in <it>TNFα </it>is associated with chronic bronchitis in AATD.</p