Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosisNISHIYAMA O, KONDOH Y, KIMURA T, KATO K, KATAOKA K, OGAWA T, WATANABE F, ARIZONO S, NISHIMURA K, TANIGUCHI H. Respirology 2008; 13: 394-399 Background and objective: Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF. Methods: Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme. Results: Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05). Conclusions: Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.

F usion genes involving ZNF384 have recently been identified in Bcell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS.

The prognosis in idiopathic pulmonary fibrosis (IPF) is poor. No therapy has been shown to prolong survival. The objective of this study was to examine the prognostic significance of dyspnoea in daily living at baseline in IPF using a simple assessment tool.93 consecutive patients with IPF, who had undergone evaluation at diagnosis, were included. The level of dyspnoea was assessed using the modified Medical Research Council (MRC) scale. The relationship between data at baseline and survival was examined.A univariate Cox proportional-hazard model showed that forced vital capacity % predicted (hazard ratio (HR) 0.965, 95% CI 0.948-0.982; p,0.0001), diffusing capacity of the lung for carbon monoxide % predicted (HR 0.978, 95% CI 0.963-0.993; p50.0041), baseline arterial oxygen tension (HR 0.963, 95% CI 0.938-0.989; p50.0060) and modified MRC score (HR 2.402, 95% CI 1.495-3.858; p50.0003) were significantly predictive of survival. All variables of the 6-min walk test, including walk distance (HR 0.995, 95% CI 0.992-0.998; p50.0020), the lowest arterial oxygen saturation measured by pulse oximetry (Sp,O 2 ) (HR 0.944, 95% CI 0.918-0.972; p,0.0001) and the Borg scale (HR 1.285, 95% CI 1.091-1.514; p50.0027), were also significant. With stepwise, multivariate Cox proportional analysis, the modified MRC score (HR 2.181, 95% CI 1.333-3.568; p50.0019) and the lowest Sp,O 2 during the 6-min walk test (HR 0.952, 95% CI 0.924-0.981; p50.0014) were the most significant. Dyspnoea in daily living, assessed with the modified MRC scale at baseline, provides additional prognostic information for patients with IPF.

It is important to be aware of the possibility of acute exacerbation of interstitial pneumonia following SLB even after an apparently uneventful immediate postoperative course. The asymmetric image findings suggest that intraoperative respiratory management is a possible etiologic factor.

This study concerns the significance of nuclear/cytoplasmic expression of beta-catenin and mutation of the beta-catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of 'palisading cells', 'stellate cells', and 'ghost cells'. In addition, 'whorl-like arrays' of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta-catenin predominantly in cohesive cells within the whorl-like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki-67 was almost absent. The cohesive cells in the whorl-like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta-catenin accumulation showed heterozygous one-base substitution mutation of the beta-catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl-like arrays and ghost cells rather than as simple proliferation stimuli.

No abstract

In this study, mitochondria migrated to a perinuclear region in the cytoplasm in herpes simplex virus (HSV)-infected cells. HSV infection did not promote the expression of cytochrome c oxidase subunit 2 but did promote that of stress-responsive HSP60, both of which are known to be components of mitochondria. The levels of cellular ATP and lactate and mitochondrial membrane potential were maintained for at least 6 h but decreased at the late stage of infection. It was also found that the UL41 and UL46 gene products, both of which are known to be tegument proteins, accumulated in the perinuclear region. The clustering of mitochondria and the accumulation of tegument proteins were completely blocked by the addition of nocodazole and vinblastine. These results suggest that mitochondria respond to the stimulation of HSV infection, migrating with tegument proteins along microtubules to a site around the nucleus, and maintain function until at least the middle stage of infection.Mitochondria are well-known multifunctional organelles of which eukaryotic cells usually contain several hundred, widely spread throughout the cytoplasm. Although mitochondria have their own genome, transcription-translation equipment and replication system, nuclear-encoded gene products are indispensable for mitochondria in order to function and, conversely, eukaryotic cells could not survive without mitochondria. They have thus evolved very intimate and complicated communication systems, some parts of which remain elusive.This study focused on the effects of herpes simplex virus (HSV) infection on mitochondria. Since mitochondria play prominent roles in supplying energy, regulating calcium levels and controlling apoptotic cell death, processes that are critically important for cell mortality, it is important to study virus-