DNA Damage Sensor γ

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC

Three dimensional motion analyses for rehabilitation version of Awa Odori exercise and the expectancy of physical effects

‘Awa Odori Exercise -Rehabilitation version- was developed in 2006 for the new trial of physical exercise for the aging and the impaired person with lower balance performance in Tokushima prefecture, Japan. Public relations of this exercise had been spreading over Tokushima since then. The characteristics of the exercise were highly familiar with most of people in Tokushima because of popularity in original ‘Awa Odori’. This study proposed the efficacies of Awa Odori Exercise as a rehabilitation exercise. This exercise expected the flexible balance reinforcements and the substitution for walking training with prevention of fall, bedridden and participating restriction for the old people, also promoting the health in Tokushima

Gait and posture assessments of a patient treated with deep brain stimulation in dystonia using three-dimensional motion analysis systems

Kinesiologic analysis of gait disorders, postural instabilities and abnormal movements is quite difficult to assess objectively by clinical observation, such as by specific scale and video recordings. In this study, we reported one of the aspects of the usefulness of three-dimensional motion analysis (Vicon Systems, Oxford, United Kingdom), which can measure inclusive data of movement disorders and substitute for conventional assessments. A 49-year-old man who had various dystonic symptoms, mainly on his left side of the body, responded well to deep brain stimulation (DBS). The examination quantified how the involuntary movements or other symptoms with dystonia changed before and after treatments

Idiopathic Normal-Pressure Hydrocephalus: Temporal Changes in ADC during Cardiac Cycle

Normal-pressure hydrocephalus (NPH) is characterized by a clinical triad of ataxia, incontinence, and dementia, as well as dilated ventricles but normal cerebrospinal fluid (CSF) pressures. In patients with NPH, CSF shunt placement is effective for improving these symptoms (1). NPH has attracted attention as one of the few treatable causes of dementia. Diagnosis of idiopathic NPH (INPH) without a known cause of communicating hydrocephalus, including subarachnoid hemorrhage or meningitis, is particularly difficult (2). Moreover, to clarify the cause of NPH, accurately diagnose NPH, and identify appropriate patients for shunt surgery, several tests have been proposed, including cisternography, the CSF tap test, resistance measures, external lumbar drainage, and intracranial pressure recording, in addition to clinical findings and conventional imaging diagnosis with x-ray computed tomography or magnetic resonance (MR) imaging (3–6). It has also been reported (7) that a single standard for the prognostic evaluation of patients with INPH was lacking and that supplemental tests could increase the predictive accuracy of the prognosis. The CSF tap test is a particularly reliable examination, but it is invasive and has low sensitivity. It has been proposed that MR imaging CSF flow studies can be used to noninvasively obtain information about intracranial mechanical properties in INPH (eg, intracranial compliance) (2,8–12). However, the diagnostic utility of this latter method is still not established.Arterial inflow into the cranium induces venous and CSF outflow and displacement of the intracranial spinal cord during the cardiac cycle, resulting in pulsatile brain motion (12–14). Brain pulsation (ie, bulk motion) reportedly can give rise to artifactual phase dispersion and may lead to overestimation of the apparent diffusion coefficient (ADC) (15,16). Brockstedt et al (17) reported that ADC was not changed significantly during the cardiac cycle with the single-shot echo-planar imaging (EPI) sequence widely used in diffusion MR imaging. However, they analyzed only two delay times (100 and 400 msec) between the R peaks in the cardiac cycle. To more completely analyze ADC changes during the cardiac cycle, our own group has previously evaluated the temporal change in ADC during the entire cardiac cycle by using an electrocardiographically (ECG)-triggered single-shot diffusion EPI sequence to minimize bulk motion effect. As a result, we revealed in a previous study that white matter ADC changed significantly over the cardiac cycle and that such changes were synchronized with the arterial inflow (volume loading) at systole (18). We further hypothesize that changes in ADC during the cardiac cycle are related to the biomechanical properties of intracranial tissues; hence, observed temporal changes in ADC in diseases such as INPH that are characterized by low intracranial compliance (12) may well be different than those in other diseases. Therefore, the purpose of our study was to determine whether temporal changes in ADC over the cardiac cycle were different in patients with INPH as compared with patients with ex vacuo ventricular dilatation and healthy control subjects

Relationship between Barthel Index scores during the acute phase of rehabilitation and subsequent ADL in stroke patients

The Barthel Index (BI) cannot be used to measure initial stroke severity or by extension, to stratify patients by severity in acute stroke trials because most patients are bedbound in the first few hours after stroke, either by their deficit or by medical directive. Our objectives were to clarify the threshold of acute BI for use in the prediction of subsequent independence in activities of daily living (ADL) and to assist in the definition of acute stroke rehabilitation goals. Subjects comprised 78 patients out of 191 inpatients admitted with acute stroke at our hospital during 2006-2007. The BI ADL score was divided into 2 ranges (BI≧60 and≦40), in a process similar to previous studies. During the acute period (from onset to approximately 3 weeks), all patients with a BI≧40 could improve their ADL in 6 months. Patients with a BI≦40 exhibited two ADL recovery outcomes (improved and no change) at 6 months. We also found that the skill level of basic activities related to standing was significant indicator of BI improvement (P<0.001). BI scores determined at approximately 3 weeks were reliable predictors of ADL disabilities at 6 months

Antisense PMO Found in Dystrophic Dog Model Was Effective in Cells from Exon 7-Deleted DMD Patient

BACKGROUND: Antisense oligonucleotide-induced exon skipping is a promising approach for treatment of Duchenne muscular dystrophy (DMD). We have systemically administered an antisense phosphorodiamidate morpholino oligomer (PMO) targeting dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in Japan (CXMD(J)) lacking exon 7 and achieved recovery of dystrophin in skeletal muscle. To date, however, antisense chemical compounds used in DMD animal models have not been directly applied to a DMD patient having the same type of exon deletion. We recently identified a DMD patient with an exon 7 deletion and tried direct translation of the antisense PMO used in dog models to the DMD patient's cells. METHODOLOGY/PRINCIPAL FINDINGS: We converted fibroblasts of CXMD(J) and the DMD patient to myotubes by FACS-aided MyoD transduction. Antisense PMOs targeting identical regions of dog and human dystrophin exons 6 and 8 were designed. These antisense PMOs were mixed and administered as a cocktail to either dog or human cells in vitro. In the CXMD(J) and human DMD cells, we observed a similar efficacy of skipping of exons 6 and 8 and a similar extent of dystrophin protein recovery. The accompanying skipping of exon 9, which did not alter the reading frame, was different between cells of these two species. CONCLUSION/SIGNIFICANCE: Antisense PMOs, the effectiveness of which has been demonstrated in a dog model, achieved multi-exon skipping of dystrophin gene on the FACS-aided MyoD-transduced fibroblasts from an exon 7-deleted DMD patient, suggesting the feasibility of systemic multi-exon skipping in humans

p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma

Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC). As the number of patients studied to date has been limited, clinically useful prognostic biomarkers of NASH-related HCC have not been available. In this study, we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC. p27 has been regarded as a prognostic factor in various types of cancer patients. A total of 22 cases with NASH-related HCC were analyzed for p27 protein expression, and phosphorylation at threonine 157 (T157) and serine 10 (S10) by immunohistochemical analysis. The correlation of p27 with tumor characteristics, disease-free survival (DFS), and overall survival was analyzed. p27 expression was decreased in 13 HCCs (59%), and was significantly correlated with enlarged tumor size (p = 0.01) and increased cell proliferation (p &lt; 0.01). Phospho-p27 at T157 and S10 was detected in four (18%) and seven (32%) cases, respectively, and patients positive for phospho-p27 (S10) showed reduced DFS (hazard ratio 7.623, p = 0.016) by univariate analysis. Further studies with more patients are required to verify the usefulness of p27 as a biomarker for predicting tumor recurrence in NASH patients