Distribution of adherens junction mediated by VE-cadherin complex in rat spleen sinus endothelial cells

The splenic sinus endothelium regulates the passage of blood cells through the splenic cord. The goal of the present study was to assess the localization of vascular endothelial (VE)-cadherin, β-catenin, and p120-catenin in the sinus endothelial cells of rat spleen and to characterize the presence and distribution of adherens junction formation mediated by the cadherin-catenin complex. Immunofluorescent microscopy of tissue cryosections demonstrated that VE-cadherin, β-catenin, and p120-catenin were localized in the junctional regions of adjacent endothelial cells. Double-staining immunofluorescent microscopy for VE-cadherin and β-catenin revealed colocalization at junctional regions. Transmission electron microscopy of thin sections of sinus endothelial cells treated with Triton X-100 clearly showed adherens junctions within the plasma membrane. Adherens junctions were located at various levels in the lateral membranes of adjacent endothelial cells regardless of the presence or absence of underlying ring fibers. Immunogold electron microscopy revealed VE-cadherin, β-catenin, and p120-catenin in the juxtaposed junctional membranes of adjacent sinus endothelial cells. Double-staining immunogold microscopy for VE-cadherin and β-catenin and for VE-cadherin and p120-catenin demonstrated colocalization to the junctional membranes of adjacent endothelial cells. Immunolabeling was evident at various levels in the lateral junctional membranes and was intermittently observed in the sinus endothelium. These data suggest that adherens junctions, whose formation appears to be mediated by VE-cadherin-catenin complexes, probably regulate the passage of blood cells through the spleen. This work was supported by a Grant-in-Aid for Scientific Research (C), Japan     

Endothelial and virgultar cell formations in the mammalian lymph node sinus: endothelial differentiation morphotypes characterized by a special kind of junction (<Emphasis Type="Italic">complexus adhaerens</Emphasis>)

The lymph node sinus are channel structures of unquestionable importance in immunology and pathology, specifically in the filtering of the lymph, the transport and processing of antigens, the adhesion and migration of immune cells, and the spread of metastatic cancer cells. Our knowledge of the cell and molecular biology of the sinus-forming cells is still limited, and the origin and biological nature of these cells have long been a matter of debate. Here, we review the relevant literature and present our own experimental results, in particular concerning molecular markers of intercellular junctions and cell differentiation. We show that both the monolayer cells lining the sinus walls and the intraluminal virgultar cell meshwork are indeed different morphotypes of the same basic endothelial cell character, as demonstrated by the presence of a distinct spectrum of general and lymphatic endothelial markers, and we therefore refer to these cells as sinus endothelial/virgultar cells (SEVCs). These cells are connected by unique adhering junctions, termed complexus adhaerentes, characterized by the transmembrane glycoprotein VE-cadherin, combined with the desmosomal plaque protein desmoplakin, several adherens junction plaque proteins including α- and β-catenin and p120 catenin, and components of the tight junction ensemble, specifically claudin-5 and JAM-A, and the plaque protein ZO-1. We show that complexus adhaerentes are involved in the tight three-dimensional integration of the virgultar network of SEVC processes along extracellular guidance structures composed of paracrystalline collagen bundle “stays”. Overall, the SEVC system might be considered as a local and specific modification of the general lymphatic vasculature system. Finally, physiological and pathological alterations of the SEVC system will be presented, and the possible value of the molecular markers described in histological diagnoses of autochthonous lymph node tumors will be discussed. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Cost‐effectiveness of Endoscopic Surveillance for Gastric Intestinal Metaplasia

Background: Patients with intestinal metaplasia (IM) are at increased risk for gastric cancer. Endoscopic surveillance has been shown to anticipate cancer diagnosis in an earlier stage. Cost‐effectiveness of endoscopic surveillance in IM patients is unknown. To assess the efficacy and cost‐effectiveness of an yearly endoscopic surveillance in patients with IM. Methods: A decision analysis model was constructed in order to compare a strategy of performing an EGD every year for a 10‐year period (surveillance strategy) following a new diagnosis of IM to a policy of nonsurveillance in a simulated cohort of 10,000 American patients. A 1.8% 10‐year cumulative incidence of gastric cancer in IM patients was estimated from the literature. Endoscopic surveillance was simulated to downstage the detected cancers by 58–84%. Costs of EGD and cancer care were estimated from Medicare reimbursement data. The main outcome measurement was the incremental cost‐effectiveness ratio. Results: The number of EGDs required to detect one cancer and to prevent one gastric cancer‐related death in the surveillance arm were 556 and 3738, respectively. The incremental cost‐effectiveness ratio of endoscopic surveillance as compared to a nonsurveillance policy was $72,519 per life‐year gained (5–95% percentiles Monte Carlo analysis: $54,843–$98,853). At sensitivity analysis, cancer incidence and the rate of downstaging were the most important variables. Conclusions: According to our simulation, the relatively high risk of cancer in patients with IM and the substantial efficacy of endoscopic surveillance in reducing cancer‐related mortality would support the cost‐effectiveness of an endoscopic surveillance program in patients with IM. Further research is needed before implementing it in the clinical practice.     

Fibroblast growth factor 10 is required for proper development of the mouse whiskers

Fibroblast Growth Factor (FGF) signaling is known to play an important role during cutaneous development. To elucidate the role of FGF10 during whisker formation, we examined the expression of Fgf10 in normal developing whiskers and phenotypes of Fgf10-deficient whiskers. Fgf10 is first expressed in the maxillary process, lateral and medial nasal processes, then in the mesenchymal cells underneath the future whisker placodes, and in the surrounding mesenchyme of developing whiskers. Fgf10-null whiskers exhibit a significant decrease in number and their structure is disorganized as revealed by scanning electron microscopy. Hair follicle marker genes such as Sonic hedgehog, Patched, and Patched 2 are aberrantly expressed in the mutant whiskers. Thus, FGF10 is required for proper whisker development mediated by SHH signaling in the mouse.     

中华绒螯蟹窦腺神经末梢及X-器官神经分泌细胞的类型

在电子显微镜下观察了性未成熟的中华绒螯蟹黄蟹的窦腺及X－器官的超微结构。X－器官位于眼柄神经节终髓的腹外侧,与窦腺位置斜相对,窦腺主要由神经分泌细胞的末梢和胶质细胞组成。神经末梢含有大量的膜结构包围的颗粒、线粒体、粗面内质网和许多电子透明的小泡,末梢外周有时可见指状突起。依据颗粒的大小、形状、电子致密度以及胞质特征,可区分出6种类型的窦腺神经末梢及7种X－器官神经分泌细胞。观察了末梢中神经分泌颗粒的胞吐作用方式的释放过程,并且尝试对窦腺不同末梢中的颗粒及X－器官神经分泌细胞中的颗粒作了比较,发现二者之间具有较好的对应性,即电子致密度无大的变化,形态特征相似,只是大小稍有增加。     

Tachykinin-like immunoreactivity in the sinus venosus of the dogfish (Scyliorhinus canicula)

The sinus venosus of the elasmobranch heart is characterized by the presence of large bundles of unmyelinated nerve fibres that bulge into the cardiac lumen, below the endocardium. In the dogfish (Scyliorhinus canicula), these fibres contain numerous dense-core membrane-bounded granules of about 200 nm in diameter. Most intramural ganglion cells of the sinus venosus also show densely packed granules similar to those found in the subendocardial fibres. We have observed strong substance-P-like immunoreactivity in the large fibre bundles and in the perikarya of the ganglion cells. Preabsorption of the antisera with fragment 7–11 of substance P has shown that the antisera recognize the tachykinin canonic sequence. Our findings suggest that an undetermined tachykinin is secreted in the elasmobranch heart, and that it is probably released into the blood stream in the context of a little-known neuroendocrine system.     

鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎的治疗效果及对患者嗅觉功能和鼻黏膜形态的影响

摘要 目的：探讨鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎的治疗效果及对患者嗅觉功能和鼻黏膜形态的影响。方法：选取我院2019年1月到2022年12月收治的80例慢性鼻窦炎患者作为研究对象,分为观察组与对照组,各40例。对照组患者采取单纯鼻内镜手术治疗,观察组患者在术前应用枸地氯雷他定治疗1个月后再行鼻内镜手术,对比两组患者的临床治疗效果,治疗前后炎症因子水平,内镜下鼻粘膜形态量化评分,嗅觉功能与糖精试验时间。结果：两组患者治疗总有效率对比无差异（P＞0.05）;治疗后两组患者IL-6、IL-1、TNF-α相关炎症因子水平均降低,且观察组较对照组低（P＜0.05）;治疗前两组患者鼻漏、结痂、瘢痕、黏膜水肿、息肉、脓性分泌物等情况内镜下鼻粘膜形态量化评分对比无明显差异（P＞0.05）,治疗后两组患者鼻漏、结痂、瘢痕、黏膜水肿、息肉、脓性分泌物等情况内镜下鼻粘膜形态量化评分均降低,且观察组较对照组低（P＜0.05）;治疗前两组患者嗅觉识别阈值、糖精试验时间对比无明显差异（P＞0.05）,治疗后两组患者嗅觉识别阈值、糖精试验时间均降低,且观察组低于对照组（P＜0.05）。结论：鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎具有显著临床疗效,同时能够降低患者术后炎症因子水平,改善鼻黏膜形态,提升纤毛运动功能与嗅觉功能,值得临床应用推广。     

Fine structure of the neurohemal sinus gland of the shore crab,Carcinus maenas,and immuno-electron-microscopic identification of neurosecretory endings according to their neuropeptide contents

Summary The sinus gland of the shore crab, Carcinus maenas, is a compact assembly of interdigitating neurosecretory axon endings abutting upon the thin basal lamina of a central hemolymph lacuna. Four types of axon endings are distinguishable by the size distribution, shape, electron density and core structure of their neurosecretory granules. One additional type of axon ending is characterized by electron-lucent vacuoles and vesicles. The axon profiles are surrounded by astrocyte-like glial cells. Various fixations followed by epoxy- or Lowicrylembedding were compared in order to optimize the preservation of the fine structure of the granule types and the antigenicity of their peptide hormone contents. By use of specific rabbit antisera, the crustacean hyperglycemic, molt-inhibiting, pigment-dispersing, and red-pigment-concentrating hormones were assigned to the four distinct granule types which showed no overlap of immunostaining. Epi-polarization microscopy and ultrathin section analysis of immunogold-stained Lowicrylembedded specimens revealed that immunoreactivity to Leu-enkephalin and proctolin is co-localized with moltinhibiting hormone immunoreactivity in the same type of granule. The size and core structure of the immunocytochemically identified granule types vary little with the different pretreatments but, in some cases, to a statistically significant extent. The present results are compared with those from earlier studies of sinus glands in different crustaceans. The methods of granule identification used in this study supplement the classical approach in granule typing; they are easier to perform and more reliable for the analysis of release phenomena in identified secretory neurons supplying the neurohemal sinus gland.     

Identification of neuropeptides from the decapod crustacean sinus glands using nanoscale liquid chromatography tandem mass spectrometry

Neurosecretory systems are known to synthesize and secrete a diverse class of peptide hormones which regulate many physiological processes. The crustacean sinus gland (SG) is a well-defined neuroendocrine site that produces numerous hemolymph-borne agents including the most complex class of endocrine signaling molecules--neuropeptides. As an ongoing effort to define the peptidome of the crustacean SG, we determine the neuropeptide complements of the SG of the Jonah crab, Cancer borealis, and the Maine lobster, Homarus americanus, using nanoflow liquid chromatography electrospray ionization quadrupole time-of-flight (ESI-QTOF) MS/MS. Numerous neuropeptides were identified, including orcokinins, orcomyotropin, crustacean hyperglycemic hormone (CHH), CHH precursor-related peptides (CPRPs), red pigment concentrating hormone (RPCH), beta-pigment dispersing hormone (beta-PDH), proctolin and HL/IGSL/IYRamide. Among them, two novel orcokinins were de novo sequenced from the SG of H. americanus. Three CPRPs including a novel isoform were sequenced in H. americanus. Four new CPRPs were sequenced from the SG of C. borealis. Our results show that structural polymorphisms in CPRPs (and thus the CHH precursors) are common in Dendrobranchiata as well as in Pleocyemata. The evolutionary relationship between the CPRPs is also discussed.     

Discrimination of normal gastric mucosa from Helicobacter pylori gastritis using standard endoscopes and a single observation site: studies in children and young adults

Background. In the Helicobacter pylori‐negative normal stomach, collecting venules are visible in the gastric corpus as numerous minute points. This finding has been termed ‘regular arrangement of collecting venules’ (RAC). The aim of the present study was to investigate the reliability of the presence of the RAC pattern for discrimination of normal gastric mucosa from H. pylori gastritis in pediatric patients. Methods. Fifty‐two consecutive children, adolescents and young adults (male:female 24 : 28; median age 15 years, range 8–29 years) referred for endoscopy and assessed for H. pylori infection were prospectively studied. The lower lesser curvature of the corpus near the incisura was evaluated for the RAC pattern using a standard endoscope with the tip close to, but not in contact with, the gastric surface. Gastric biopsies were taken after the endoscopic observation. Results. In all the 29 RAC‐positive patients, active H. pylori gastritis was absent, whereas H. pylori gastritis was found in 20 of 23 RAC‐negative patients (86.9%). Conclusions. Identification of the RAC pattern at the lower lesser curvature of the corpus using close observation with a standard endoscope proved to be an effective and practical marker to discriminate normal histology from H. pylori gastritis among both children and young adults. Absence of the RAC pattern should prompt gastric mucosal biopsies despite otherwise normal‐appearing gastric mucosa.