Association of mannose‐binding lectin gene polymorphisms with Kawasaki disease in the Japanese

Objective: Kawasaki disease (KD) is a systemic vasculitis in childhood; its etiology is unknown. The possibility that KD is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. Young children rely on their innate immune system for protection against virus and micro‐organisms. Human mannose binding lectin (MBL) is a C‐type serum lectin synthesized by the liver as an acute phase protein and it plays an important role in the innate immune system. Here, we investigate the relationship between the MBL gene polymorphisms and the occurrence of KD in the Japanese population. Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD. Results: The MBL codon‐54 polymorphism frequency of heterozygote (GGC/GAC) and promoter variants were significantly higher in the KD group than that in the control group (P < 0.05). Neither group showed codon 52 nor 57 polymorphisms. Conclusion: It is possible that mutations of the MBL gene might be related to the trigger of the pathogenesis of Kawasaki disease.     

小鼠骨髓基质细胞Kusa-A1成骨分化中CBF1的作用

目的揭示CBF1在骨髓基质细胞Kusa-A1成骨分化过程中的作用。方法采用基因转染法建立CBF1稳定过表达细胞系Kusa-A1/CBF1,检测其成骨活性。指标包括细胞钙沉积能力、碱性磷酸酶活性、体外钙化结节(CN)形成、实时PCR测定细胞骨钙素(OC)和骨桥蛋白(OPN)基因表达、蛋白印迹检测细胞RANKL蛋白。最后用报告基因法检测CBF1对HES1启动子活性的影响。结果经RT-PCR和Western blot鉴定,Kusa-A1/CBF1细胞建立成功。与对照细胞系Kusa-A1/host相比,Kusa-A1/CBF1细胞的钙沉积能力、CN形成能力均显著提高;Kusa-A1/CBF1细胞OC和OPN基因表达和RANKL蛋白水平明显高于对照细胞。瞬时转染Notch的细胞内结构域NICD促进HES1的启动子活性,这一作用被CBF1强烈抑制。结论CBF1可以促进Kusa-A1的成骨分化,该作用至少部分是通过影响Notch信号实现的。     

Predictors of Seizure Outcome after Repeat Pediatric Epilepsy Surgery: Reasons for Failure,Sex, Electrophysiology,and Temporal Lobe Surgery

Considering that seizure freedom is one of the most important goals in the treatment of epilepsy, repeat epilepsy surgery could be considered for patients who continue to experience drug-resistant seizures after epilepsy surgery. However, the chance of seizure freedom is reported to be below 50% after reoperation for failed epilepsy surgery. This study aimed to elucidate the predictive factors for seizure outcomes after repeat pediatric epilepsy surgery. In all, 39 pediatric patients who underwent repeat curative epilepsy surgery between 2008 and 2020 at our institution were retrospectively studied. The relationship between preoperative clinical factors and postoperative seizure freedom at the last follow-up was statistically evaluated. The mean age at the first surgery was 5.5 years (0–16). The etiology of epilepsy was malformation of cortical development in 33 patients. The average time to seizure recurrence after the first surgery was 6.4 months (range, 0–26 months). In all, 16 patients (41.0%) achieved seizure freedom after the second surgery. Seven patients underwent a third surgery, and three (42.9%) achieved seizure freedom. Overall, 19 patients achieved seizure freedom after repeat epilepsy surgery (48.7%). Female sex, surgical failure due to technical limitations, congruent electroencephalography (EEG) findings, lesional magnetic resonance imaging (MRI) and Rt-sided surgery were predictive of seizure freedom, and surgery limited to the temporal lobe was predictive of residual seizures, as determined in the multivariate analysis. The reoperation of failed epilepsy surgery is challenging. Consideration of the above predictive factors can be helpful in deciding whether to reoperate on pediatric patients whose initial surgical intervention failed.     

Primary Experiences with Robot-assisted Navigation-based Frameless Stereo-electroencephalography: Higher Accuracy than Neuronavigation-guided Manual Adjustment

The use of robot-assisted frameless stereotactic electroencephalography (SEEG) is becoming more common. Among available robotic arms, Stealth Autoguide (SA) (Medtronic, Minneapolis, MN, USA) functions as an optional instrument of the neuronavigation system. The aims of this study were to present our primary experiences with SEEG using SA and to compare the accuracy of implantation between SA and navigation-guided manual adjustment (MA). Seventeen electrodes from two patients who underwent SEEG with SA and 18 electrodes from four patients with MA were retrospectively reviewed. We measured the distance between the planned location and the actual location at entry (De) and the target (Dt) in each electrode. The length of the trajectory did not show a strong correlation with Dt in SA (Pearson''s correlation coefficient [r] = 0.099, p = 0.706) or MA (r = 0.233, p = 0.351). De and Dt in SA were shorter than those in MA (1.99 ± 0.90 vs 4.29 ± 1.92 mm, p = 0.0002; 3.59 ± 2.22 vs 5.12 ± 1.40 mm, p = 0.0065, respectively). SA offered higher accuracy than MA both at entry and target. Surgical times per electrode were 38.9 and 32 min in the two patients with SA and ranged from 51.6 to 88.5 min in the four patients with MA. During the implantation period of 10.3 ± 3.6 days, no patients experienced any complications.     

Longitudinal change in depressive symptoms among healthcare professionals with and without COVID-19 vaccine hesitancy from October 2020 to June 2021 in Japan

This study aimed to compare the longitudinal change in depressive symptoms among healthcare professionals in Japan who are willing to receive novel coronavirus disease (COVID-19) vaccination and those who are unwilling to receive COVID-19 vaccination. The baseline survey was conducted in October 2020 (Survey time 1: T1); respondents in T1 were invited to participate in May 2021 (Survey time 2: T2). Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Group comparisons of the estimated mean of PHQ-9 score at T1 and T2 were estimated by the analysis of covariance. In T1, 597 participants (response rate: 4.4%) completed all questions. In T2, 211 participants (follow up rate: 35.3%) completed all questions. The group and time interaction effect was significant (F(1, 207)=3.9, p=0.049); depressive symptoms were worse among healthcare professionals who were unwilling to receive vaccination than among those who were willing to receive vaccination. This study showed that depressive symptoms were worse among healthcare professionals who were unwilling to receive COVID-19 vaccination than those who are willing to receive COVID-19 vaccination. This suggests that it is important to take care of healthcare professionals who are unwilling to receive vaccination to prevent mental health deterioration.     

The Transport Mechanism of an Organic Cation,Disopyramide, by Brush-border Membranes. Comparison Between Renal Cortex and Small Intestine of the Rat

Abstract— The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H⁺ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H⁺ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H⁺ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (K_m and V_max of 680 μm and 1·25 nmol (mg protein)^?1/30 s, respectively). The stimulation of disopyramide uptake by an outward H⁺ gradient in rat intestinal brush-border membrane was due to an interior negative H⁺-diffusion potential. A K⁺-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.     

Effect of Application Volume and Area on the Absorption of Phenol Red,as a Model Drug,from the Liver Surface in Rats

To determine the influence of the method of administration of a pharmaceutical formulation we have examined the importance of application volume and area in the absorption of phenol red, as a model drug, from the rat-liver surface. When 1 mg phenol red was applied to the rat-liver surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cylindrical glass cell (i.d. 9 mm), the shape of the plasma concentration profile differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the absorption-rate constant K_a obtained was inversely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm²). Furthermore, the permeability coefficient P_app derived from K_a did not depend on application area, indicating no difference in the absorption characteristics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal administration to the rat-liver surface for clinical application, increasing the application volume resulted in the delayed disappearance of phenol red from the plasma. However, the difference was not as marked as that obtained by use of the glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate P_app. Consequently, we speculate that absorbability can be estimated precisely by consideration of application volume and area.