Scanning Electron Microscopic Study of the Collagen Sheath of the Human Thyroid Gland and Its Disorders

A cell-maceration/scanning electron microscope (SEM) method was employed to demonstrate the collagen sheath around follicles (perifollicular sheath) of the human thyroid gland and its disorders. In the normal thyroid gland, the follicles were surrounded by spherical collagen sheaths composed of a framework of thick collagen bands 1-5 μm in width and fine solitary collagen fibrils 50-70 nm in diameter. In benign thyroid diseases (Graves\u27 disease, Hashimoto\u27s thyroiditis and adenomatous goiter), the perifollicular sheaths differed in size and in shape according to the disease, but they were always composed of thick collagen bands and fine fibrils as in the normal thyroid. On the other hand, the spaces surrounded by the perifollicular sheaths varied markedly in size in follicular adenoma, were small in oxyphilic adenoma, and irregularly shaped in embryonal adenoma. In all these adenomas, the perifollicular sheaths were mainly composed of fine fibrils 35-45 nm in diameter. In follicular carcinoma, the size and shape of the space surrounded by the perifollicular sheaths were irregular. In papillary adenocarcinoma, the collagen sheaths showed a papillary pattern. In medullary carcinoma, tumor nests were surrounded by well developed collagen sheaths. In all these carcinomas, the collagen sheaths were mainly composed of fine collagen fibrils 32-45 nm in diameter. In adenomas and follicular carcinoma, the perifollicular sheaths frequently had large holes through which the spaces surrounded by the collagen sheaths connected to each other. Such holes were, however, rare in the normal thyroid and benign non-neoplastic thyroid diseases

Epigenetic Regulation of Adipocyte Differentiation by a Rho Guanine Nucleotide Exchange Factor, WGEF

Epigenetic regulation, including DNA methylation, plays an important role in several differentiation processes and possibly in adipocyte differentiation. To search for genes that show methylation change during adipogenesis, genome-wide DNA methylation analysis in insulin-induced adipogenesis of 3T3-L1 preadipocyte cells was performed using a method called microarray-based integrated analysis of methylation by isoschizomers (MIAMI). The MIAMI revealed that Hpa II sites of exon 1 in a Rho guanine nucleotide exchange factor 19 (ARHGEF19; WGEF) gene were demethylated during adipocyte differentiation of 3T3-L1 cells. Deletion of the region containing cytosine-guanine (CpG) sites that showed methylation change suppressed transcriptional activity in the reporter assay, indicating that this region regulates WGEF transcription. WGEF expression in 3T3-L1 cells was reduced during adipocyte differentiation, and high-fat diet-induced obese mice also showed lower expression of WGEF gene than control mice in white adipose tissue. Additionally, forced expression of WGEF in 3T3-L1 cells down-regulated the expression of adipogenic marker genes and inhibited the adipogenic program. This study clarified that adipogenesis was regulated by WGEF expression through DNA methylation change

One Argonaute family member, Eif2c2 (Ago2), is essential for development and appears not to be involved in DNA methylation

AbstractTo elucidate the epigenetic role of RNAi in mammals, we disrupted the gene for Eif2c2 (Ago2), which works as the sole slicer of RNAi in the Argonaute family. In mice, disruption of Eif2c2 leads to embryonic lethality early in development after the implantation stage. This phenotype is completely different from that in a previous report, but somewhat similar to the disruption of Dicer1, another important component of RNAi. We also show that Eif2c2 is not required for the maintenance of DNA methylation in imprinted genes, centromeric repeats, and Xist. This suggests that developmental defects in the Eif2c2-deficient mouse are caused not at the transcriptional level, but rather at the posttranscriptional level through the miRNA–protein complex

Syncope and loss of consciousness after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: Prevalence and characteristics in long-term follow-up

Background Syncope is a significant prognostic factor in patients with Brugada syndrome (BrS). However, the risk of ventricular arrhythmia in patients with nonarrhythmic loss of consciousness (LOC) is similar to that in asymptomatic patients. LOC events after implantable cardioverter-defibrillator (ICD) implantation may provide insights into underlying causes of the initial LOC episode. Objective The purpose of this study was to examine LOC characteristics following ICD implantation. Methods We retrospectively analyzed 112 patients with BrS (mean age 47 years; 111 men) who were treated with an ICD. The patients were classified into 3 groups based on symptoms at implantation: asymptomatic (35 patients); LOC (46 patients); and ventricular tachyarrhythmia (VTA) (31 patients). We evaluated the incidence and cause of LOC during long-term follow-up after ICD implantation. Results During mean follow-up of 12.2 years, 41 patients (37%) experienced LOC after ICD implantation. Arrhythmic LOC occurred in 5 asymptomatic patients, 14 LOC patients, and 16 patients with VTA. Nonarrhythmic LOC, similar to the initial episode, occurred after ICD implantation in 6 patients with prior LOC (2 with neurally mediated syncope and 4 with epilepsy). Most epileptic patients experienced LOC during rest or sleeping, and did not show an abnormal encephalogram during initial evaluation of the LOC episodes. Conclusion After ICD implantation, 13% of patients had nonarrhythmic LOC similar to the initial episode. Accurate classification of LOC based on a detailed medical history is important for risk stratification, although distinguishing arrhythmic LOC from epilepsy-related LOC episodes can be challenging depending on the circumstances and characteristics of the LOC event

Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome

Background: The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results: Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. Conclusions: The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS

Dicer Is Required for Maintaining Adult Pancreas

Dicer1, an essential component of RNA interference and the microRNA pathway, has many important roles in the morphogenesis of developing tissues. Dicer1 null mice have been reported to die at E7.5; therefore it is impossible to study its function in adult tissues. We previously reported that Dicer1-hypomorphic mice, whose Dicer1 expression was reduced to 20% in all tissues, were unexpectedly viable. Here we analyzed these mice to ascertain whether the down-regulation of Dicer1 expression has any influence on adult tissues. Interestingly, all tissues of adult (8–10 week old) Dicer1-hypomorphic mice were histologically normal except for the pancreas, whose development was normal at the fetal and neonatal stages; however, morphologic abnormalities in Dicer1-hypomorphic mice were detected after 4 weeks of age. This suggested that Dicer1 is important for maintaining the adult pancreas

Dicer Is Required for Maintaining Adult Pancreas

Dicer1, an essential component of RNA interference and the microRNA pathway, has many important roles in the morphogenesis of developing tissues. Dicer1 null mice have been reported to die at E7.5; therefore it is impossible to study its function in adult tissues. We previously reported that Dicer1-hypomorphic mice, whose Dicer1 expression was reduced to 20% in all tissues, were unexpectedly viable. Here we analyzed these mice to ascertain whether the down-regulation of Dicer1 expression has any influence on adult tissues. Interestingly, all tissues of adult (8–10 week old) Dicer1-hypomorphic mice were histologically normal except for the pancreas, whose development was normal at the fetal and neonatal stages; however, morphologic abnormalities in Dicer1-hypomorphic mice were detected after 4 weeks of age. This suggested that Dicer1 is important for maintaining the adult pancreas

A Case of Cholesterol Crystal Embolization with Hemorrhagic Intestinal Ulcer

Cholesterol crystal embolization (CCE) is a rare systemic embolism caused　by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during　vascular manipulation such as vascular surgery or endovascular catheter manipulation, or　due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal　ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history　of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI)　for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed　tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and　bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small　intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small　intestine was performed. A histopathological examination indicated that small intestine　obstruction was caused by CCE. A histopathological examination indicated that small intestinal　obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular　manipulation, CCE should also be considered

卵黄レシチンのハブ毒およびすい臓リパーゼによる酵素分解について(農芸化学部門)

卵黄レシチン分子における脂肪酸の分布の解明に利用する目的で, ハブ毒レシチナーゼAおよびすい臓リパーゼ製品(ステアプシン)中のレシチナーゼを用いて同レシチンおよびリゾレシチンの酵素分解を行ない, 生成物を調査した。ステアプシンはレシチナーゼAまたはBとしての作用を有すると同時にレシチナーゼD(ホスホリパーゼC)としても働き, ジーおよびモノグリセリドを生成する。またこの際脱離する脂肪酸は飽和酸が多く, ハブ毒レシチナーゼAによつて脱離する脂肪酸がほとんど不飽和酸であるのと対照的であり, 両酵素のエステル結合切断位置が異なることを示唆している。その他蛇毒で生成したリゾレシチンの酸化反応や, すい臓リパーゼのグリセリド分解における特性などから考えて, 少なくともハブ毒レシチナーゼAの作用点もグリセリル基のβ-位置を主とするものと推定できる。By means of Trimeresurus flavoviridis venom and a pancreatic lipase preparation, the location of the fatty acids in egg lecithin and in egg lysolecithins prepared by enzymic and chemical hydrolysis has been studied. Fatty acids and phosphorylcholine were principally liberated from the egg lecithin by the pancreatic lipase preparation, leading to the formation of lysolecithins and di-and monoglycerides. The major components of the monoglycerides were β-monoglycerides. In this lipase hydrolysis, the predominance of saturated acids in the liberated fatty acids and of unsaturated acids in monoglycerides and lysolecithins was observed in contrast to the hydrolysis of lecithin by the snake venom which removed most of the component unsaturated acids. By oxidation with bromine, the lysolecithin obtained by venom hydrolysis gives a carbonyl compound which seems to be probably β-ketolysolecithin. These results show that the venom enzyme specifically hydrolyzes the β-linked fatty acids, and therefore the saturated fatty acids are located mainly on the α\u27-position, while the unsaturated acids are mainly on the β-position of egg lecithin

Evaluation of intra-ductal cancer spread using contrast superb micro-vascular imaging (SMI) : a case report

Currently, breast conserving surgery has been adopted to treat more than half of all breast cancer patients in Japan. When performing breast-conserving surgery, an appropriate margin needs to be determined for radical cure. The resection volume influences the esthetic outcome, but a cancer-positive resection stump is also important risk factor of local recurrence. Additionally, the degree of cancer progression influences the surgical method, so understanding the appropriate resection margin is necessary for the surgeons. We report here on a 50- year old patient whose intra-ductal cancer progression was shown, as predicted, by contrast SMI (superb micro-vascular imaging). A one-cm size tumor mass was palpable with a clear boundary. B-mode ultrasound confirmed the presence of a breast duct towards the nipple from the tumor mass. Using contrast SMI, an accelerated blood flow was detected around the duct, which suggested intra-ductal progression. The pathological results also showed intra-ductal progression to the nipple from the tumor. Around the progression area, a meandering vessel was found and the vessel was able to be visualized by contrast SMI