Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea‐acanthocytosis

Chorea‐acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult‐onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real‐time quantitative PCR and long‐range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. © 2011 Wiley‐Liss, Inc.     

定量质子磁共振波谱对鉴别良性与恶性脑膜瘤的价值(英文)

本研究致力于探讨定量质子磁共振波谱(MRS)对鉴别良性与恶性脑膜瘤的价值。研究利用1.5T磁共振仪,对23例脑膜瘤(良性组(WHO I级)19例,恶性组(WHOⅡ～Ⅲ级)4例)进行单体素MRS检查(PRESS序列,TR/TE=2000ms/68,136,272ms),通过指数衰减模型估计组织水和胆碱(Choline,Cho)的T2弛豫时间,并以组织水为内参照计算Cho的绝对浓度,然后按MRS体素内坏死或囊变组织的比例对Cho浓度进行校正。研究发现,良、恶性脑膜瘤的组织水T2弛豫时间分别是(105±41)ms和(151±42)ms,差异有显著性(P=0.033)。良、恶性脑膜瘤的Cho T2弛豫时间分别是(242±73)ms和(316±102)ms,无显著差异(P=0.105)。良、恶性脑膜瘤的Cho浓度在校正前分别是(2.86±0.86)mmol/kg wet weight和(3.53±0.60)mmol/kg wet weight,在校正后分别是(2.98±0.93)mmol/kg wet weight和(4.58±1.22)mmol/kg wet weight,校正后差异具有显著性(P=0.019)。研究...     

Exophytic cavernous hemangioma arising from the right ventricle: Report of a rare case

Cardiac hemangioma is relatively rare, accounting for approximately 1–3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.     

Histological alterations following fine-needle aspiration for parathyroid adenoma: Incidence and diagnostic problems

This study aimed to clarify the histological alterations following fine-needle aspiration for parathyroid adenoma and discuss the occurrence of diagnostic problems. Among the 392 patients with parathyroid adenoma who underwent resection, fine-needle aspiration was performed for 21 (5.1%) parathyroid adenoma nodules. Histological findings that were significantly more frequent in cases that underwent fine-needle aspiration were considered histological alterations following fine-needle aspiration for parathyroid adenoma, including the following six findings: thick fibrous capsule (71.4%), multilayered fibrous capsules (14.3%), capsular pseudo-invasion (42.9%), fibrous bands (57.1%), hemosiderin deposition (14.3%), and tumor implantation (14.3%). Eighteen parathyroid adenoma nodules (85.7%) exhibited one or more of the six findings. Tumor cells and adipocytes entrapped within the thick fibrous capsule were occasionally observed. The fibrous bands were frequently connected to the thick fibrous capsule. The number of passes, duration between fine-needle aspiration and resection, tumor size, and purpose of fine-needle aspiration were not related to the incidence of histological findings. Because of the histological alterations following fine-needle aspiration for parathyroid adenoma that can be easily mistaken for signs of atypical adenoma or parathyroid carcinoma, we recommend that the six findings be excluded from pathological findings indicating atypical adenoma or parathyroid carcinoma in patients with preoperative fine-needle aspiration.     

Preventive effect of monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associate antigen-1 on murine spontaneous fetal resorption

PROBLEM: Are cell adhesion molecules involved in the murine model of immunologically‐mediated spontaneous abortion?
METHOD OF STUDY: Pregnant CBA/J female mice mated with DBA/2 male mice were injected with monoclonal antibodies (MAbs) to intercellular adhesion molecule‐1 (ICAM‐1) and leukocyte function‐associate antigen‐1 (LFA‐1). On day 13 of gestation, viable and resorbed embryos were counted. Natural killer (NK) cell activity in the spleen, mixed lymphocyte reactions (MLR), mixed lymphocyte‐placenta reactions (MLPR), and levels of interferon (IFN)‐Γ were assayed.
RESULTS: Significant suppression of fetal resorption was observed by the injection of MAb to ICAM‐1 and LFA‐1. NK cell activity and the MLR anti‐(CBA/J×DBA/2)F1 were reduced in the antibody‐treated CBA/J spleen. Moreover, the level of IFN‐Γ was significantly lower in the MLPR supernatants from the antibody‐treated group than those of the control group.
CONCLUSIONS: One mechanism in the murine model of spontaneous abortion may be through the interaction of cell adhesion molecules, which may modulate NK cell activities and cytokine production.     

Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A

A defect of the gene for p94 (calpain 3), a skeletal muscle-specific calpain, is responsible for limb girdle muscular dystrophy type 2A (LGMD2A), or 'calpainopathy', which is an autosomal recessive and progressive neuromuscular disorder. To study the relationships between the physiological functions of p94 and the etiology of LGMD2A, we created transgenic mice that express an inactive mutant of p94, in which the active site Cys129 is replaced by Ser (p94:C129S). Three lines of transgenic mice expressing p94:C129S mRNA at various levels showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wild-type mice of the same age had almost none. There was more p94 protein produced in aged transgenic mice muscles and it showed significantly less autolytic degradation activity than that of wild-type mice. Although no necrotic-regenerative fibers were observed, the age and p94:C129S expression dependence of the phenotypes strongly suggest that accumulation of p94:C129S protein causes these myopathy phenotypes. The p94:C129S transgenic mice could provide us with crucial information on the molecular mech-anism of LGMD2A.     

Clinical evaluation of the Gyro Pump C1E3 as a cardiopulmonary bypass pump

The Gyro Pump C1E3 is a new centrifugal pump with numerous features, including a ceramic pivot bearing system, secondary vanes, and an eccentric inlet port. To evaluate its biocompatibility, antithrombogenicity, and produced hemolysis, we used the Gyro Pump during cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG) cases to compare it with the BioMedicus pump. From September 1998 to February 1999, 30 consecutive patients underwent CABG under conventional CPB. Fifteen patients were supported by the Gyro Pump C1E3 (Group G), and the remaining 15 patients, by a BioMedicus BP-80 pump (Group B). In both groups, flow rate was equivalent. Blood samples were taken as follows: preoperative, 60 minutes after the end of the procedure, and at postoperative days (POD) 0, 1, and 2. We evaluated the plasma free hemoglobin (free Hb) as an indication of hemolysis; beta-thromboglobulin (beta-TG) and platelet factor four (PF-4) as an indication of platelet deterioration; C3, C4, CH50 for complement activation; coagulation parameters, fibrinolytic factor, thrombomodulin, nitric oxide (NO), and endothelin as an indication of endothelial deterioration. This was the first clinical sized Gyro Pump CIE3. De-airing from the pump was easily accomplished via the eccentric oblique inlet port. The system, including its console, was easily and simply controlled. Perioperative laboratory data were not markedly changed in either group with demonstrated equivalence for biocompatibility and hemolysis. After pumping, no thrombus formation or pivot wear were observed inside the pump. This atraumatic, small centrifugal pump appears well suited not only for CPB but also for circulatory support.     

Anionic polymerization of monomers containing functional groups, 14. Anionic polymerizations of aryl 4‐vinylbenzoates

Anionic polymerizations of phenyl ( 2a ), 4‐methoxyphenyl ( 2b ), 2‐methylphenyl ( 2c ), 2‐tert‐butylphenyl ( 2d ), 3,5‐di‐tert‐butylphenyl ( 2e ), 2,6‐dimethylphenyl ( 1f ), 2,6‐diisopropylphenyl ( 2g ), 2,6‐di‐tert‐butyl‐4‐methylphenyl ( 2h ), and 2,6‐di‐tert‐butyl‐4‐methoxyphenyl ( 2i ) 4‐vinylbenzoates were carried out in THF at –78°C with diphenylmethylpotassium and oligo(α‐methylstyryl)lithium and ‐dipotassium. No apparent polymerizations of 2a – 2e occurred probably due to the inherent side reactions such as nucleophilic attack of the anionic initiators toward the ester carbonyl groups. On the other hand, the polymerizations of 2f – 2i , the monomers possessing bulky aryl ester substituents, certainly proceeded to afford the polymers in quantitative yields. The molecular weight distribution (MWD) of poly( 2f ) was broad (M_w/M_n = 1.3–1.8), indicating partial side reactions during the course of the polymerization. By contrast, the resulting poly( 2g – 2i ) possessed narrow MWDs (M_w/M_n = 1.1) and predicted molecular weights based on the molar ratios between monomers to initiators. It was thus demonstrated that the steric hindrance around the ester carbonyl group was essential to obtain polymers having well‐defined chain structures via controlled anionic polymerizations of aryl 4‐vinylbenzoates. Novel tailored block copolymers, polyisoprene‐block‐poly( 2h ), poly( 2h )‐block‐polystyrene‐block‐poly( 2h ), poly(tert‐butyl methacrylate)‐block‐poly( 2h ), and poly( 2h )‐block‐poly(2‐isopropenylbenzoxazole) were synthesized by the sequential copolymerization of 2h and the corresponding comonomers. It was elucidated from the results of block copolymerization that anionic polymerizability of 2h was apparently higher than that of styrene because of the electron‐withdrawing effect of the COOAr substituent.     

Moving Mesh Method for Reconstructing Some Spread Sources in the Brain

The purpose of this paper is to propose a new algorithm for the analysis of biomagnetic field data obtained from magnetoencephalography (MEG) measurements. This new method overcomes two major problems faced by the current method of data analysis. The first problem is the need to determine the number of sites of brain activity before calculations can be performed. The second problem is inability of the analysis to provide any information regarding the volume of the brain activity. The new data analysis method, called the Moving Mesh Method (MMM), is capable of analyzing MEG data without the need to determine the number of sources beforehand. In addition, the MMM determines the location of brain activity as a three dimensional volume, instead of as a point source of activity. The MMM uses an iterative method of calculating the position of the sources to achieve greater accuracy, and a regularized g-inverse matrix to stabilize its solution. The feasibility of the MMM was examined by two methods. First, a computer simulation was used to confirm the MMM's capability to analyzing MEG data. In the second experiment, the MMM was applied to analyze somatosensory evoked fields obtained using a new imaging system (Shimadzu Biomagnetic Imaging System, Model-100). From the interpretation of the results, we have concluded that the MMM is a feasible method of biomagnetic data analysis.