Molecular Genetic Analysis of HLA—DR and HLA—DQ Genes Among Anti—U1-70-kd Autoantibody Positive Connective Tissue Disease Patients

Objective. We have recently found that the presence of autoantibodies against the 70-kd polypeptide of U1 RNP (U1-70-kd) is associated with HLA—DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA—DR and DQ genes among patients with autoantibodies against U1-70-kd. Methods. The polymerase chain reaction (PCR), sequence-specific oligonucleotide hybridization, and solid-phase direct DNA sequencing of PCR-amplified DNA were utilized to analyze HLA—DRB1, DRB5, DQA1, and DQB1 genes. Results. A comprehensive analysis of HLA—DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30—32, 70, and 73 of HLA—DRB1 on disease-associated haplotypes. Conclusion. A common cluster of shared amino acids, or a shared epitope, identified within HLA—DRB1 among anti—U1—70-kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1—70-kd antigen.     

Properties of Magnetic Garnet Films for Flexible Magneto-Optical Indicators Fabricated by Spin-Coating Method

Non-destructive testing using a magneto-optical effect is a high-resolution non-destructive inspection technique for a metallic structure. It is able to provide high-spatial resolution images of defects. Previously, it has been difficult to fabricate flexible magneto-optical sensors because thermal treatment is necessary to crystallize the magnetic garnet. Therefore, it was not possible to apply magneto-optical imaging to complicated shapes in a test subject, such as a curved surface. In this study, we developed a new process for deposition of the magnetic garnet on the flexible substrate by applying the magnetic garnet powders that have already undergone crystallization. In this new process, as it does not require thermal treatment after deposition, flexible substrates with low heat resistance can be used. In this paper, we report our observations of the optical properties, magnetic hysteresis loop, crystallizability and density of the particles on the flexible substrate deposited by the spin-coating method.     

Involvement of thiol proteases in galactosialidosis

The activities of Z-Phe-Arg-NMec(ZPA) hydrolase, cathepsin B and cathepsin H and the concentration of endogenous thiol protease inhibitor in fibroblasts from patients with galactosialidosis were found not to be significantly different from those in control fibroblasts. Culture for 5 days with thiol protease inhibitors such as leupeptin, E-64 or Z-Phe-Phe-CHN2 partially restored the beta-galactosidase activity of fibroblasts from patients, but did not affect the beta-galactosidase activity of fibroblasts from control subjects. However, culture with leupeptin, but not other protease inhibitors, increased the ZPA hydrolase and cathepsin B activities of fibroblasts from both patients and controls 2- to 4-fold. Sephadex G-75 chromatography showed that the activity of high molecular weight ZPA hydrolase, which was initially predominant in fibroblasts, decreased markedly during their culture with leupeptin, while the activities of lower molecular weight ZPA hydrolase and cathepsin B increased about 5-fold. These results suggest that high molecular weight ZPA hydrolase, which is presumably cathepsin J, degrades beta-galactosidase, and that the defect in galactosialidosis is impaired protection of beta-galactosidase from degradation.     

Teratogenicity of Antiepileptic Drugs: Is the Prevention Possible?

Abstract: To assess the relative contribution of antiepileptic drugs (AEDs) toward the occurrence of congenital malformation, two prospective studies (previous and present) were compared. In the present subjects of 145 cases, the total daily dose of AEDs (drug score) in each case was decreased as much as possible, and polypharmacy was changed to monopharmacy before conception where it was possible. The incidence of malformations significantly decreased from 13.5% to 6.2% (p = 0.031) by the change in drug regimen. The drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy were statistically different between the two study groups. Even after the correction of the data by the last three factors, the difference in the incidence of malformation did not disappear, while it disappeared if data were corrected either by the drug score or number of AEDs. These results suggest that the possibility of prevention of AED related malformations is possible by an improvement in AED therapy.     

Clinical characteristics of upper airway resistance syndrome

Polysomnographic findings and clinical symptoms were investigated in 14 cases of upper airway resistance syndrome. The mean scores of the Epworth sleepiness scale and self-rating depression scale in eight cases were 13.5 and 38.6, respectively. The mean sleep latency of the multiple sleep latency test in four cases was 10.2 min. Seven cases were treated with continuous positive airway pressure (CPAP), and one with hormone replacement therapy. The most common symptom was daytime sleepiness. Five cases had hypertension. CPAP reduced increasing negative esophageal pressure (Pes) and frequency of EEG arousals, and improved hypertension in one case. Hormone replacement therapy ameliorated increasing negative Pes and clinical symptoms.     

Caenorhabditis elegans senses protons through amphid chemosensory neurons: proton signals elicit avoidance behavior

Acidic pH is known to cause pain sensation through nociceptive neurons as well as taste transduction in mammals. Caenorhabditis elegans avoids an acidic environment (pH lower than approximately 4.0) formed by organic or inorganic acids. This avoidance behavior was dependent on multiple amphid chemosensory neurons, and inhibited by a mutation of capsaicin receptor homologue, and by the addition of amiloride and ruthenium red (inhibitors of proton-gated Na+ channels and capsaicin receptors, respectively). These results indicate that C. elegans recognizes protons as a nociceptive stimulus, through multiple neurons, which elicits avoidance behavior. It is of special interest that a system similar to that of mammalian signal transduction is responsible for this nematode's acid avoidance.     

Miller Fisher Syndrome Following Vaccination against SARS-CoV-2

After BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination, a 30-year-old man developed bilateral lateral gaze palsy, diplopia, absent tendon reflexes, and ataxic gait. Serum anti-GQ1b and anti-GT1a immunoglobulin G (IgG) antibodies were strongly positive. Based on those findings, he was diagnosed with Miller Fisher syndrome (MFS). Intravenous immunoglobulin therapy was administered, and his symptoms fully recovered within approximately 3 months. To the best of our knowledge, this is the first report to describe the development of MFS after COVID-19 mRNA vaccination.     

Severe Sinus Bradycardia in Anorexia Nervosa-A Case Report

A case of anorexia nervosa complicated with severe sinus bradycardia and low T3 syndrome was reported.     

Differentiating Dementia with Lewy Bodies from Alzheimer's Disease Using the Fall Risk Evaluation Questionnaire

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer''s disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.