Clinical characterization of adults with Asperger's syndrome assessed by self-report questionnaires based on depression,anxiety, and personality

Diagnosing Asperger's syndrome (AS) in adults is difficult and efficient indicators for a precise diagnosis are important in the clinical setting. We examined the clinical characteristics of AS in 129 adults (median age, 32.0 years [range, 19–57]; 102 men and 27 women; AS group (n = 64; median age, 32.0 years [range, 19–50]; 50 men and 14 women), control group (n = 65; median age, 32.0 years [range, 19–57]; 52 men and 13 women) through administration of the Japanese version of the Autism-Spectrum Quotient (AQ) and the Japanese version of the Hospital Anxiety and Depression Scale (HADS), the Liebowitz Social Anxiety Scale (L-SAS), and the NEO Five-Factor Inventory (NEO-FFI). AQ, HADS, and L-SAS scores, and the ‘Neuroticism’ scores of the NEO-FFI were significantly higher in adults with AS than in controls. The ‘Extraversion’, ‘Agreeableness’, and ‘Conscientiousness’ scores of the NEO-FFI were significantly lower in adults with AS than in controls. Total score of the AQ correlated with the ‘Anxiety’ subscale score of the HADS and the ‘Extraversion’, ‘Openness’, and ‘Conscientiousness’ subscale scores of the NEO-FFI in adults with AS, but not in controls. The findings demonstrated that the AQ and other scales could be used to elucidate the clinical characteristics of AS in adults.     

The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome

INTRODUCTION: Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). METHODS AND RESULTS: In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). CONCLUSIONS: Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome.     

Bone morphogenetic protein 2 induced differentiation toward superficial epithelial cells in the gastric mucosa

Background Epithelial–mesenchymal interactions are important for maintenance of the gastrointestinal tract mucosa. Moreover, diffusible factors from the underlying mesenchyme control the proliferation and differentiation of the epithelial cells. However, the details of the associated signaling remain unknown. Methods Two novel cell lines, designated MSE1 (mouse stomach epithelium) and MSMF1 (mouse stomach myofibroblast) cells, were established from mouse glandular stomach and cocultured in three-dimensional collagen gels in vitro. Results MSE1 cells formed dramatic branching tubular structures upon coculture with MSMF1 cells. In contrast, they formed spherical cyst structures in the absence of fibroblast support or the presence of Swiss 3T3 cells. Since bone morphogenetic protein 2 (BMP2) was expressed by MSMF1 cells but not Swiss 3T3 cells, we investigated whether it induced the morphological differentiation. Addition of BMP2 to MSE1 cells induced the formation of branching tubular structures, even in the absence of MSMF1 cells. Noggin, a BMP2 antagonist, blocked the MSMF1-induced tubular branch formation by MSE1 cells. MSE1 cells were induced to express mRNA of MUC5AC, an important marker for gastric superficial epithelium in the upper part of pits, upon branching tubule formation after BMP2 addition. Coculture with MSMF1 cells or BMP2 addition induced Smad1 phosphorylation in MSE1 cells. Furthermore, BMP2 inhibited MSE1 cell proliferation in MTS assays and suppressed AKT phosphorylation. Conclusions BMP2 stimulated MSE1 cells to form branching duct-like structures and differentiate toward superficial epithelium in three-dimensional cocultures in vitro, suggesting that it may act as a morphogen and differentiation inducer in epithelial–mesenchymal interactions of gastric mucosa.     

Operative treatment of bilateral hip dislocations in a child with metatropic dysplasia

We present a case of bilateral hip dislocations with metatropic dysplasia. Radiographic features such as narrow thorax, dense wafer vertebral bodies, narrowing interpedicular distances, kyphoscoliosis, crescent-shaped iliac wings, dumbbell-shaped tubular bones, and inferiorly directing lesser trochanter conform to the findings of metatropic dysplasia. Hip dislocations were misdiagnosed by ultrasonographic and radiographic hip screening, owing to the severely deformed femoral heads and acetabulums. The diagnosis of hip dislocations became possible by magnetic resonance imaging. The bilateral hip dislocation was reduced by open reduction of the hip joints and femoral derotation varus osteotomies.     

Cellular effects of manufactured nanoparticles: effect of adsorption ability of nanoparticles

Nanoparticles are important industrial materials. However, many nanoparticles show biological effects, including toxic activity. Metal ion release is the most important factor affecting the biological effects of nanoparticles. In addition, nanoparticles have large adsorption ability. The adsorption ability, in particular protein adsorption to nanoparticles, has an effect on cellular uptake and cellular metabolisms. Moreover, the adsorption ability of nanoparticles causes artificial effects in in vitro systems. Consequently, accurate determination of released or secreted proteins such as lactate dehydrogenase and cytokines adsorbed to nanoparticles is affected. In addition, artificial effects cause overestimation or underestimation of the cytotoxicity of nanoparticles. Therefore, measurement of the protein adsorption of nanoparticles is important. Some methods for the determination of the adsorption to nanoparticles have been suggested. The flow field-flow fractionation method is one of the efficient techniques for determining proteins on the surface of nanoparticles. The cellular effects caused by nanoparticles should be carefully considered.     

Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells

Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the motor neurons degenerate. The discovery of new drugs for treating ALS has been hampered by a lack of access to motor neurons from ALS patients and appropriate disease models. We generate motor neurons from induced pluripotent stem cells (iPSCs) from familial ALS patients, who carry mutations in Tar DNA binding protein-43 (TDP-43). ALS patient-specific iPSC-derived motor neurons formed cytosolic aggregates similar to those seen in postmortem tissue from ALS patients and exhibited shorter neurites as seen in a zebrafish model of ALS. The ALS motor neurons were characterized by increased mutant TDP-43 protein in a detergent-insoluble form bound to a spliceosomal factor SNRPB2. Expression array analyses detected small increases in the expression of genes involved in RNA metabolism and decreases in the expression of genes encoding cytoskeletal proteins. We examined four chemical compounds and found that a histone acetyltransferase inhibitor called anacardic acid rescued the abnormal ALS motor neuron phenotype. These findings suggest that motor neurons generated from ALS patient-derived iPSCs may provide a useful tool for elucidating ALS disease pathogenesis and for screening drug candidates.     

Research on neurodegenerative diseases using induced pluripotent stem cells

Induced pluripotent stem cells (iPSC) are derived from somatic cells. These somatic cells have had their gene expression experimentally reprogrammed to an embryonic stem cell‐like pluripotent state, gaining the capacity to differentiate various cell types in the three embryonic germ layers. Thus, iPSC technology makes it possible to obtain neuronal cells from any human cells. iPSC can be generated from various kinds of somatic cells and from patients with neurodegenerative diseases. Disease modelling using iPSC technology would elucidate the pathogenesis of such diseases and contribute to related drug discoveries. In this review, we discuss the recent advances in iPSC technology as well as its potential applications.