Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation

Investigations of chromosomal rearrangements in patients with mental retardation (MR) are particularly informative in the search for genes involved in MR. Here we report a family with concomitant duplications of methyl CpG binding protein 2 (MECP2) at Xq28 and ATRX (the causative gene for X-linked alpha thalassemia/mental retardation) at Xq21.1 detected by array-comparative genomic hybridization. The alterations were observed in a 25-year-old man who inherited them from his mother, who showed a normal phenotype and completely skewed X-chromosome inactivation, and also in his cousin, a 32-year-old man. The proband and his cousin showed severe MR, muscular hypotonia, recurrent respiratory infections and various other features characteristic of MECP2 duplication syndrome. However, the proband also had cerebellar atrophy never reported before in MECP2 duplication syndrome, suggesting that his phenotypes were modified through the ATRX duplication in an additive or epistatic manner.     

A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.     

Simultaneous imaging using Si-PM-based PET and MRI for development of an integrated PET/MRI system

The silicon photomultiplier (Si-PM) is a promising photo-detector for PET for use in magnetic resonance imaging (MRI) systems because it has high gain and is insensitive to static magnetic fields. Recently we developed a Si-PM-based depth-of-interaction PET system for small animals and performed simultaneous measurements by combining the Si-PM-based PET and the 0.15 T permanent MRI to test the interferences between the Si-PM-based PET and an MRI. When the Si-PM was inside the MRI and installed around the radio frequency (RF) coil of the MRI, significant noise from the RF sequence of the MRI was observed in the analog signals of the PET detectors. However, we did not observe any artifacts in the PET images; fluctuation increased in the count rate of the Si-PM-based PET system. On the MRI side, there was significant degradation of the signal-to-noise ratio (S/N) in the MRI images compared with those without PET. By applying noise reduction procedures, the degradation of the S/N was reduced. With this condition, simultaneous measurements of a rat brain using a Si-PM-based PET and an MRI were made with some degradation in the MRI images. We conclude that simultaneous measurements are possible using Si-PM-based PET and MRI.     

17β-Oestradiol inhibits doxorubicin-induced apoptosis via block of the volume-sensitive Cl(-) current in rabbit articular chondrocytes

BACKGROUND AND PURPOSE

Chondrocyte apoptosis contributes to disruption of cartilage integrity in osteoarthritis. Recent evidence suggested that the volume-sensitive organic osmolyte/anion channel [volume-sensitive (outwardly rectifying) Cl⁻ current (I_Cl,vol)] plays a functional role in the development of cell shrinkage associated with apoptosis (apoptotic volume decrease) in several cell types. In this study, we investigated the cellular effects of 17β-oestradiol on doxorubicin-induced apoptotic responses in rabbit articular chondrocytes.

EXPERIMENTAL APPROACH

Whole-cell membrane currents and cross-sectional area were measured from chondrocytes using a patch-clamp method and microscopic cell imaging, respectively. Caspase-3/7 activity was assayed as an index of apoptosis.

KEY RESULTS

Addition of doxorubicin (1 µM) to isosmotic bath solution rapidly activated the Cl⁻ current with properties similar to those of I_Cl,vol in chondrocytes. Doxorubicin also gradually decreased the cross-sectional area of chondrocytes, followed by enhanced caspase-3/7 activity; both of these responses were totally abolished by the I_Cl,vol blocker DCPIB (20 µM). Pretreatment of chondrocytes with 17β-oestradiol (1 nM) for short (approximately 10 min) and long (24 h) periods almost completely prevented the doxorubicin-induced activation of I_Cl,vol and subsequent elevation of caspase-3/7 activity. These effects of 17β-oestradiol were significantly attenuated by the oestrogen receptor blocker ICI 182780 (10 µM), as well as the phosphatidyl inositol-3-kinase (PI3K) inhibitors wortmannin (100 nM) and {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 (20 µM). Testosterone (10 nM) had no effect on the doxorubicin-induced Cl⁻ current.

CONCLUSIONS AND IMPLICATIONS

17β-Oestradiol prevents the doxorubicin-induced cell shrinkage mediated through activation of I_Cl,vol and subsequent induction of apoptosis signals, through a membrane receptor-dependent PI3K pathway in rabbit articular chondrocytes.     

Prospective randomized controlled trial investigating the type of sutures used during hepatectomy

AIM: To determine whether absorbable sutures or non-absorbable sutures are better in preventing surgical site infection (SSI), in this paper we discuss the results of a randomized clinical trial which examined the type of sutures used during hepatectomy. METHODS: All hepatic resections performed from January 2007 to November 2008 at the Department of Surgery at Iizuka Hospital in Japan were included in this study. There were 125 patients randomly assigned to an absorbable sutures (Vicryl) group or non-absor...     

Late-onset mental deterioration and fluctuating dystonia in a female patient with a truncating MECP2 mutation

A 26-year-old woman with psychomotor developmental delay since late infancy showed rapid deterioration of her psychomotor abilities at the 11 years of age. She had gained the ability to verbally express herself and perform motor activities such as running and dancing in early childhood, but she lost the ability to verbally communicate and was unable to walk independently after this period. She also presented with dystonia in the right extremities, which markedly fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC (p.P399QfsX4) near the 3'-terminal of the coding region. The phenotype of this patient corresponds to the rare, unestablished variant of "late childhood deterioration" in MECP2-related disorders. For the first time, MECP2 mutation was confirmed to be the genetic basis of this condition.     

Neuropsychological profile of children with cryptogenic localization-related epilepsy and its association with age at onset

The aim of this study was to investigate the neuropsychological profile of children with cryptogenic localization-related epilepsy (CLRE). Neuropsychological evaluations were performed in 16 CLRE children and 14 children with idiopathic localization-related epilepsy (ILRE) for control within 8 months (average 2.1 months) of initial seizure. The neuropsychological tests used in this study are as follows: the Wechsler Intelligence Scale for Children-Third Edition, Wechsler Intelligence Scale for Children-Revised, and Wechsler Preschool and Primary Scale of Intelligence. Age at onset and test differed significantly between CLRE and ILRE, while the duration between onset and test and the number of seizures before test did not. No marked difference was observed in the neuropsychological profile between 2 groups; however, the discrepancy between VIQ and PIQ was significantly larger in CLRE than in ILRE. This discrepancy was negatively correlated with age at the time of seizure onset (r = -0.615, and p = 0.011). The laterality in discrepancy between VIQ and PIQ was associated with the dominance of interictal discharge. In conclusion, children with lower age at the time of seizure onset were likely to have had a larger discrepancy between VIQ and PIQ.     

Malignant brain tumor with rhabdoid features in an adult

Rhabdoid tumor (RT) of the central nervous system is an uncommon and aggressive neoplasm that usually affects pediatric patients. Currently, these tumors are classified as malignant RT or atypical teratoid/RT. Another entity of intraparenchymal brain tumor with a rhabdoid component is the extremely rare rhabdoid glioblastoma. A 23-year-old woman presented with a malignant RT in the right thalamus. The tumor was adjacent to the right lateral ventricle and was partially resected. Histological examination revealed prominent proliferation of rhabdoid cells, which is consistent with a diagnosis of malignant RT; the typical features of glioblastoma were not observed. The tumor cells stained positively for integrase interactor-1 and glial fibrillary acidic protein. Therefore, the tumor may have originated from glial components. Genetic analysis using comparative genomic hybridization showed a deoxyribonucleic acid copy-number gain on chromosome 7 but not on chromosome 22. The tumor did not respond to chemotherapy or radiotherapy, and the patient survived for only 4 months after surgery. The present case of malignant RTs shows certain similarities with those of rhabdoid glioblastoma. Further accumulation and analysis of data, including data from genetic analyses, may lead to the identification of a new type of malignant RT.     

Dural cyst at the foramen magnum

A 69-year-old male presented with a rare dural cyst manifesting as numbness and pain in the limbs. Magnetic resonance imaging revealed a mass anterior to the medulla oblongata appearing as low intensity on T(1)-weighted and high intensity on T(2)-weighted imaging, with no enhancement. A cystic lesion ventral to the medulla oblongata was removed via the lateral suboccipital transcondylar approach. Histological examination showed the wall of the cyst consisted of fibrous connective tissue with a dense zone and a loose zone, similar to the structure found in the dura mater. The lesion was diagnosed as dural cyst. Dural cysts can be defined as cyst with the wall consisting of dura mater-like fibrous tissue, and attached to the dura mater. The origin of the present dural cyst was considered to be congenital.     

Molecular mechanism of fatty degeneration in rotator cuff muscle with tendon rupture

Fatty degeneration often occurs in rotator cuff muscle with tendon rupture. However, the molecular mechanism underlying this change has not been fully clarified yet. We investigated the gene expression of Wnt10b and adipogenic marker gene, PPARγ and C/EBPα in C2C12 myogenic cell line under inhibition of Wnt10b by adipogenic induction medium, isobutylmethylxanthine, dexamethasone, and insulin (MDI). The role of Wnt‐signal was confirmed by adding Lithium chloride (LiCl), which mimics Wnt signaling to the cultured cell with MDI. We also assessed the expression profiles of same genes in the rat rotator cuff tear model in vivo. MDI induced Oil red‐O staining positive adipocytes and upregulated PPARγ and C/EBPα expression. LiCl inhibited adipogenic induction of MDI. Rotator cuff muscle with tendon rupture showed positive staining for Oil red‐O. Real‐time polymerase chain reaction analyses revealed decreased expression of Wnt10b followed by increased PPARγ and C/EBPα gene expression in the supraspinatus muscle. Fatty degeneration and its molecular events were remarkably seen in the distal one‐third of the detached supraspinatus muscle versus control. Wnt signaling may regulate adipogenic differentiation both in the myoblasts in vitro and the muscle in vivo. Our results indicate that the reduction of Wnt10b in muscle with a rotator cuff tear is a key signal in fatty degeneration of the muscle. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:861–866