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.     

Bronchogenic cyst in the abdomen--a case report

A man in his thirties with epigastric pain was referred to our hospital for detailed examinations. Abdominal computed tomography showed an abdominal cystic lesion with a longest dimension of 7 cm, located behind the stomach. Endoscopic ultrasonography through the stomach showed a cystic lesion and the wall of the lesion revealed continuity to the proper muscle layer of the gastric wall. Therefore, gastric duplication was suspected and the cystic lesion was resected because of the possibility of malignancy and also for a definitive diagnosis. The cystic lesion consisted of columnar ciliated epithelium, seromucous glands, smooth muscle and cartilage and was diagnosed as a bronchogenic cyst. Bronchogenic cysts are sometimes encountered in the thoracic or mediastinal area, but abdominal bronchogenic cysts, such as the present case, are extremely rare.     

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.     

Circulation of 2 Barmah Forest Virus Lineages in Military Training Areas,Australia

During 2017–2018, Barmah Forest virus was recovered from mosquitoes trapped in military training areas in Australia and from a soldier infected at 1 of these areas. Phylogenies of the nucleotide sequences of the envelope glycoprotein gene E2 and the 3′ untranslated region suggest that 2 lineages are circulating in eastern Australia.     

Degradation patterns of different adhesives and bonding procedures

Various types of resin adhesives and procedures are available in the clinical field, so comprehensive understanding of degradation is required for each material and bonding procedure. The objective of this study was to investigate the bond durability for different adhesives and bonding procedures. Resin-dentin bonded beams were prepared with the use of two adhesives (One-Up Bond F/self-etching primer system and One Bond/total-etch adhesive) and two experimental groups for the bonding procedure (wet and dry bonding of the total-etch adhesive). Those samples were soaked in water for 24 h(control), 6 and 12 months. After the water immersion, the bond strengths were measured by the microtensile bond test, and subsequently fractography was performed with the use of SEM. Statistically significant reduction of the bond strength (p < 0.05) was apparent after 12 months of water exposure in the range 22-48% of the control. The bonding resin was eluted from the hybrid layer of the self-etching and the total-etch adhesives for the wet bonding. Micromorphological alterations were found due to the hydrolysis of collagen fibrils with the total-etch adhesive for the dry bonding mode. These pathologic alterations were in accord with the bond strength.     

Clinical aspects of patients with MCS - from the standpoint of allergy]

BACKGROUND: "Sick House Syndrome" is thought to be an illness caused by indoor environments such as allergens, bacteria and chemical compounds. But it is not yet an established clinical entity. "Sick House Syndrome" overlaps in part with Multiple Chemical Sensitivity (MCS) whose symptoms are induced by very small amount of volatile chemical compounds. METHODS: We selected possible cases of MCS from patients who visited our specially built facility for"Sick House Syndrome" by tentative criteria as follow: (1)histories of chemical compounds exposure, (2)multi-organ symptoms, (3)exclusion of other disease(s) which may be responsible for symptoms, (4)chronic symptoms. Clinical aspects of the possible cases were examined. RESULTS: Fifty out of about 130 patients were the possible cases of MCS, 38 females and 12 males, aged 15 to 71 years old. Forty two out of 50 patients (84%) had a history and/or a complication of allergic diseases. This rate is much higher than the rate of prevalence of allergic diseases in Japanese population. Allergic rhinitis was the most popular allergic disease in the possible cases. Total IgE values were relatively low, 32 patients (64%) showed the IgE value below 200 IU/ml. No patients showed anti-formaldehyde IgE antibody. Decreased reactivity and decreased sensitivity of histamine release from peripheral blood were observed after challenge tests with chemical compounds. CONCLUSION: Allergic reactions can not be the causative mechanism(s) of the MCS, which is induced by multiple and different chemical compounds. Our results, however, suggest that patients having allergic diseases may be easily suffered from MCS or MCS may strengthen symptoms of allergic diseases.     

Clinical and endoscopic features of metachronous gastric cancer with possible lymph node metastasis after endoscopic submucosal dissection and Helicobacter pylori eradication

Gastric Cancer - Several studies have reported the metachronous gastric cancers (MGCs) with possible lymph node metastasis (LNM) after endoscopic submucosal dissection (ESD) and Helicobacter pylori...     

Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation

In the treatment of arrhythmia, beta-blockers are mainly used to regulate the heart rate. However, beta-blockers are also known as drugs with an antiarrhythmic effect due to the suppression of sympathetic activity. We evaluated the antiarrhythmic effects of a highly selective beta(1)-blocker, bisoprolol, in patients with diurnal paroxysmal atrial fibrillation (P-AF). A total of 136 patients with symptomatic diurnal P-AF were enrolled. Patients were divided into a diurnal-specific P-AF group and a diurnal & nocturnal P-AF group, as well as into a bisoprolol single use group and a combined use group with an antiarrhythmic drug. The effects of bisoprolol were evaluated in 3 categories: subjective symptom improvement, quality of life (QOL) improvement, and elimination of P-AF episode in Holter electrocardiograms (ECGs). For patients with effective treatment, a long-term effect up to 24 months was evaluated. Five patients (3.7%) discontinued bisoprolol due to side effects. Following administration of bisoprolol, 109 patients (80%) experienced subjective symptom improvement, 103 patients (76%) experienced QOL improvement, and elimination of P-AF episodes in ECGs was observed in 84 patients (62%). The elimination rate of P-AF episodes in ECGs was higher in the diurnal P-AF group than in the diurnal & nocturnal P-AF group (P=0.042). There was no significant difference between the bisoprolol single use group and the combined use group. A long-term suppressive effect by bisoprolol was observed in 70 of 83 patients (84%). The results demonstrate that bisoprolol has an antiarrhythmic effect against sympathetic diurnal P-AF, improving subjective symptoms and QOL and eliminating P-AF episodes in ECGs.