Morphometric analysis of spike-wave complexes (SWCs) causing myoclonic seizures in children with idiopathic myoclonic epilepsies – A positive SWC component correlates with myoclonic intensity

AimTo elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies.Subjects and MethodsThe subjects were 8 patients, including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters of the SWCs were compared between those with MS [SWC-MS (+)] and those without MS [SWC-MS (-)], and a correlation coefficient analysis was performed between the SWC parameters and the duration of myoclonic electromyogram (EMG) potentials.ResultsA total of 155 SWC-MS (+) (range: 7 ～ 34) and 80 SWC-MS (-) (10 each as a control) were analyzed. Comparison of the parameters of the SWCs between SWC-MS (+) and SWC-MS (-) demonstrated that the depth and the width of the positive-sharp-components (PSC) in the SWC-MS (+) were significantly deeper in amplitude and longer in duration than those in the SWC-MS (-), respectively, in all 8 patients (P < 0.05), whereas the number of the polyphasic-multiple-spike-components (PMSC) and the height of negative-spike-components (NSC) were not significantly different in most of the patients, respectively. The depth and the width of PSC were also significantly correlated with the duration of myoclonic EMG potentials in all patients except one [depth of PSC (n = 7): r = 0.623 ～ 0.888; width of PSC (n = 8): r = 0.676 ～ 0.948, P < 0.05].ConclusionsThis study revealed that the depth and width of PSC of the SWC are positively correlated with the MS intensity in childhood-onset idiopathic myoclonic epilepsies and are an important neurophysiological marker to generate MS.     

Gastric adenocarcinoma of the fundic gland type shares common genetic and phenotypic features with pyloric gland adenoma

Gastric adenocarcinoma of the fundic gland type (GAFG) and pyloric gland adenoma (PGA) have recently been recognized as rare types of neoplasia. We performed comparative immunohistochemical and genetic analyses of 3 GAFGs and 12 PGAs. All of the 3 GAFGs were diffusely positive for pepsinogen‐I, MIST1 and MUC6, indicating the predominantly chief cell/mucous neck cell differentiation of these tumors. A small number of H.K‐ATPase‐positive parietal cells were also scattered. PGAs invariably exhibited diffuse MUC6 and TFF2 expression, consistent with the pyloric gland differentiation of these tumors. Ten of the 12 PGAs also unexpectedly exhibited focal expression of pepsinogen‐I and MIST1, suggesting that PGAs often show focal chief cell differentiation and phenotypically resemble mucous neck cells rather than pyloric glands. The mutation analyses revealed activating GNAS mutations, which have been reported to be frequently detected in PGAs, in two of the GAFGs. While GAFGs and PGAs are morphologically distinct lesions, our observations showed their partially overlapping immunohistochemical profiles and shared presence of GNAS mutations, in addition to their common occurrence in the fundic gland mucosa. Based on these observations, we suggest that both GAFGs and PGAs are closely related lesions characterized by a mucous neck cell/chief cell lineage phenotype.     

Does time of CCI measurement affect the evaluation of platelet transfusion effectiveness?

The measurement of corrected count increment at 1-h post-transfusion (CCI-1 h) of platelet concentrate (PC) transfusion is recommended, but in the revised Japanese Guideline (2017) it was changed to “after 10-min to 1-h”, following the revision of the guidelines from Western countries. Here, we aimed to investigate on the feasibility to apply the CCI measured at 10-min or 30-min post-transfusion as the surrogate of CCI-1 h. Peripheral blood was collected at 10-min, 30-min and 1-h post-transfusion of PC and the effectiveness of the transfusion was analyzed based on the CCI. In the period from December 2017 to February 2020, 8 patients, who received multiple PC transfusion (total 208) at our institution, were analyzed. We performed the univariate analyses to examine the relationship between CCI value and the categorical variables, p-value <0.1 was obtained for gender (p = 2.91 × 10^?19), fever after transfusion (p = 0.0163). The qualitative variables, namely measurement time (p = 0.0553), also showed p-value <0.1. Using these factors as covariates in the mixed effect model, we found that the measurement time (p = 0.0007) had a significant effect on the CCI value when looking at fixed effects. Although there is a tendency for decreased CCI values with time progression, the slope of the change in the mixed model was -0.00307, indicating that the CCI difference among the 3 measurements was small. Here we provide evidence that CCI measured at 10-min and 30-min post-transfusion give results comparable to those measured at 1-h post-transfusion, under the Japanese practice of platelet transfusion, which relies on 100 % single-donor apheresis PC, and ABO-identical whenever possible.     

The combination of ITS2 and psbA-trnH region is powerful DNA barcode markers for authentication of medicinal Terminalia plants from Thailand

Journal of Natural Medicines - The dried fruits of Terminalia plant (Combretaceae) called “Samo” have been used as herbal medicine in Thai traditional medicine. Four “Samo”...     

Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration

Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little is known about the intracellular signaling pathway of SCF/KIT-mediated cell migration. To investigate the signaling cascade, we made a series of 22 KIT mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca(2+) mobilization compared to WT. In Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration, and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719-mediated PI3K pathway in cell migration. Combination of Csk and the PI3K inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and the other is Y719-PI3K-Ca(2+) influx.     

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of “pathology-specific non-specific therapeutic drugs” and provide benefits to patients with chronic refractory cough.     

High incidence of subclinical peripheral neuropathy in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis): an electrophysiological study

OBJECTIVE: To study subclinical involvement of the peripheral nerves in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis: AM). MATERIAL AND METHODS: We carried out a nerve conduction study of the median, ulnar, tibial, and sural nerves in 21 patients with AM and in 28 patients with clinically definite or laboratory-supported definite multiple sclerosis (MS). RESULTS: The patients with AM showed a significantly higher frequency of abnormal records than the MS patients in the sensory nerve conduction study (52.4% vs. 14.3%, p = 0.0106). The frequency of abnormal records in the motor nerve conduction study in AM patients was twice as high as in MS patients (38.1% vs. 17.9%), but the difference was not statistically significant. Abnormality in the F-wave-evoked frequency in the median nerve was also significantly more common in AM patients than in MS patients (57.9% vs. 10.7%, p = 0.0016). CONCLUSIONS: These findings suggest that subclinical peripheral neuropathy is frequent in patients with AM.     

Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer

Background Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety. Methods A total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33–85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up. Results The final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred. Conclusions EUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.