Role of goblet cells in the progression of Barrett’s esophagus

正Objective To investigate the clinical pathological features of Barrett’s esophagus in China,and to study the relationship between the number of goblet cells and the severity of Barrett’s esophageal dysplasia.Methods From January 2008 to October 2018,in the Department of Gastroenterology and Hepatology,Tianjin Medical University     

Altered mechanobiology of Schlemm’s canal endothelial cells in glaucoma

Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm’s canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell—likely accounting for increased outflow resistance—that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness—and its biomechanical effects on pore formation—as a therapeutic target in glaucoma.Aqueous humor flows across the inner wall endothelium of Schlemm’s canal (SC) and generates a transendothelial pressure gradient from the cellular base to the cellular apex. From a biomechanical perspective, the direction of this gradient is remarkable considering that the endothelium of the systemic vasculature experiences a pressure gradient in precisely the opposite direction. In the healthy eye, this basal-to-apical transcellular pressure gradient is of sufficient magnitude to partially separate the SC cell from its supporting basement membrane, inflate dome-shaped structures known as giant vacuoles, and generate cellular mechanical strains exceeding 50% (Fig. 1) (1). The formation of giant vacuoles leads to substantial thinning of the SC endothelial cell and is thought to be associated with formation of pores that provide an outflow pathway across the SC endothelium (2). Although reported dysfunction of the pore formation process might be expected to affect outflow resistance and elevate intraocular pressure (IOP) (3, 4), mechanisms for such dysfunction have never before been established, in large part because SC cells from healthy eyes are so difficult to isolate technically, but also because isolated SC cells from the glaucomatous eye are a resource that has been exceedingly scarce. Here for the first time to our knowledge we show that the process of pore formation differs substantially between cells from the healthy versus the glaucomatous human eye and show, further, that this difference depends upon cytoskeletal stiffness that is altered in the glaucomatous SC cell, likely owing to altered substrate sensitivity and gene expression in these cells. Specifically, stiffer glaucomatous cells impede pore formation and thereby elevate IOP.Open in a separate windowFig. 1.Aqueous humor flow pathway. (Left) Schematic of anterior segment of eye showing the direction of aqueous humor flow in red. (Center) Enlargement of the iris-cornea angle (boxed region in left panel) to show the conventional outflow pathway. (Right) Transmission electron micrograph of endothelial cells forming the inner wall of SC; aqueous humor crosses the endothelium through pores to enter the lumen of SC. V, giant vacuoles. C is reproduced with permission from ref. 41.     

Perceptions of HIV/AIDS in One’s Community Predict HIV Testing

Using a subsample of respondents to the 2005 Los Angeles County health survey, we examined the relationship between perceptions of the seriousness of HIV/AIDS in one's community and HIV testing. We constructed a propensity score-based matched sample of three groups with differing perceptions of the seriousness of HIV in their community: high perceived seriousness, low perceived seriousness, and uncertain about seriousness. We compared HIV testing behavior in the three groups before and after using propensity score matching to control for selection on observed covariates. The unadjusted comparison showed a testing rate of 30.2?% among those perceiving high seriousness, 11.4 percentage points higher than the 18.8?% testing rate among those perceiving low seriousness. After propensity score matching, the adjusted testing difference was 7.0 percentage points (p?相似文献   

Interstitial cells of Cajal in the gut-A gastroenterologist’s point of view

Alterations of normal function of interstitial cells of Cajal （ICC） are reported in many intestinal disorders. Diagnosis of their involvement is rare （infrequent）, but necessary to propose a specifi c treatment. This article reviews the place of ICC in the pathogenesis of achalasia, gastroesophageal reflux disease, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction and slow transit constipation. Moreover we discuss the role of the Cajal cells in the development of stromal tumors of the gastrointestinal tract.     

Community Influences on Married Men’s Uptake of HIV Testing in Eight African Countries

Despite efforts to increase HIV testing in the African region, the proportion of men who report ever having been tested for HIV remains low. Research has focused on individual level determinants of women’s testing however little is known about factors associated with men’s testing behavior. This analysis investigates community influences on HIV testing among men ages 15–54, using Demographic and Health Survey (DHS) data from Chad, Ghana, Malawi, Nigeria, Tanzania, Uganda, Zambia, and Zimbabwe. Multilevel models were fitted in each country for the outcome of ever receiving an HIV test. After controlling for individual and household level factors, community level factors of demographics, economics, and behavior and knowledge remain significantly associated with HIV testing among men. The results of this analysis highlight the need to recognize the impact of community influences on men’s HIV test seeking behavior, and to harness these community factors in the design of programs aimed at encouraging the uptake of HIV testing among men in Africa.     

Improving Genetic Testing for Gitelman’s Syndrome

Gitelman’s syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman’s syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.     

IL-9-producing Th9 cells may participate in pathogenesis of Takayasu’s arteritis

Clinical Rheumatology - Takayasu’s arteritis (TAK) is a type of large vessel vasculitis which involves the aorta and its major branches. Interleukin (IL)-9 or IL-9-producing Th9 cells were...     

The role of Kupffer cells in the morphogenesis of nonalcoholic steatohepatitis – ultrastructural findings. The first report in pediatric patients

Abstract

Objective. Until now studies concerning the involvement of hepatic nonparenchymal cells (NPCs), particularly Kupffer cells/macrophages (KCs/MPs), in the pathogenesis of human nonalcoholic steatohepatitis (NASH) have been limited to adult patients; there are no similar reports referring to children. This study aimed to explore, based on ultrastructural analysis, the role of KCs/MPs in the morphogenesis of nonalcoholic steatohepatitis (NASH) in children. Material and methods. Ultrastructural investigations of KCs were conducted on liver bioptates obtained from 10 children, aged 2–14 years, with clinicopathologically diagnosed NASH. Bioptatic material was fixed in solution of paraformaldehyde and glutaraldehyde in cacodylate buffer, routinely processed for transmission-electron microscopic analysis and examined using an Opton EM microscope. Results. The current ultrastructural study revealed within the hepatic sinusoids the presence of numerous enlarged KCs with increased phagocytic activity, which reduced or blocked vascular lumen. Interestingly, the activated KCs not only contained primary and secondary lysosomes, altered mitochondria, and well-developed Golgi apparatus, but also absorbed fragments of erythrocytes. Such macrophages were frequently seen very close to the transformed hepatic stellate cells (T-HSCs) and progenitor/oval cells. Intensive fibrosis was observed in the vicinity of activated KCs/MPs. Bundles of collagen fibers were seen directly adhering to these cells and to other NPCs, especially T-HSCs. Conclusions. KCs are involved in the morphogenesis and development of pediatric NASH. Engulfment of erythrocytes by hepatic macrophages may lead to the accumulation of iron derived from hemoglobin in liver and play a role in triggering the generation of oxidative stress in the disease course.     

A kinetic scheme to examine the role of glial cells in the pathogenesis of Alzheimer’s disease

Metabolic Brain Disease - Alzheimer’s disease (AD) is a complex neurodegenerative disorder that leads to severe impairments in cognitive functions including memory and learning. An improved...     

Role of metals in Alzheimer’s disease

Metabolic Brain Disease - Metal homeostasis in the central nervous system (CNS) is a crucial component of healthy brain function, because metals serve as enzymatic cofactors and are key components...     

Testing the “garbage” accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy

Imperfect autophagic degradation of oxidatively damaged macromolecules and organelles (so-called biological garbage) is considered an important contributor to ageing and consequent death of postmitotic (non-dividing) cells, such as neurons and cardiac myocytes. In contrast, proliferating cells apparently escape senescence by a continuous dilution and repair of damaged structures during division. Postmitotic ageing can be mimicked and studied in cultures of potentially dividing cells if their mitotic activity is inhibited. To test the garbage accumulation theory of ageing, we compared survival of density-dependent growth-arrested (confluent) and proliferating human fibroblasts and astrocytes following inhibition of autophagic sequestration with 3-methyladenine (3MA). Exposure of confluent fibroblast cultures to 3MA for two weeks resulted in a significantly increased proportion of dying cells compared to both untreated confluent cultures and dividing cells with 3MA-inhibited autophagy. Similar results were obtained when autophagic degradation was suppressed by the protease inhibitor leupeptin. In 3MA- or leupeptin-exposed cultures, dying cells were overloaded with undegraded autofluorescent material. The results support a key role of biological lysosomal garbage accumulation in the triggering of ageing and death of postmitotic cells, as well as the anti-ageing role of cell division.     

Meta-analysis of Barrett’s esophagus in China

AIM:To investigate the epidemiology and characteristics of Barrett’s esophagus(BE)in China and compare with cases in the west.METHODS:Studies were retrieved from the China National Knowledge Infrastructure and PubMed databases using the terms"Barrett"and"Barrett AND China",respectively,as well as published studies about BE in China from 2000 to 2011.The researchers reviewed the titles and abstracts of all search results to determine whether or not the literature was relevant to the current topic of this research.The references listed in the studies were also searched.Inclusion and exclusion criteria for the literature were appropriately established,and the data reported in the selected studies were analyzed.Finally,a meta-analysis was performed.RESULTS:The current research included 3873 cases of BE from 69 studies.The endoscopic detection rate of BE in China was 1%.The ratio of male to female cases was 1.781 to 1,and the average age of BE patients was 49.07±5.09 years.Island-type and shortsegment BE were the most common endoscopic manifestations,accounting for 4.48%and 80.3%,respectively,of all cases studied.Cardiac-type BE was observed in 40.0%of the cases,representing the most common histological characteristic of the condition.Cancer incidence was 1.418 per 1000 person-years.CONCLUSION:Average age of BE patients in China is lower than in Western countries.Endoscopic detection and cancer incidence were also lower in China.     

The role of executive functions in older adults’ affective theory of mind

PurposeExecutive function (EF) has three subsystems: inhibition, updating, and shifting. Of these three, only inhibition is considered to be involved in affective theory of mind (ToM). This study investigated whether inhibition remains the sole driver for affective ToM in the three EF subsystems in older adults as well as in young people without functional reorganization via aging within EF.Materials and methodsThrough hierarchical multiple regression analysis, we examined how these three subsystems affect older participants’ performance in the Reading the Mind in the Eyes Test (RMET), a measure of affective ToM, after determining the effect of domain-specific cognitive (nonverbal and verbal) abilities.ResultsWe found that only inhibition influenced the participants’ performance in the RMET, with effects from nonverbal (fluid) ability but not from verbal ability.ConclusionsResults showed that inhibition continues to be essential for affective ToM after aging decline, and functional reorganization via aging is less likely to occur within EF.     

It’s not all equal: a multiphasic theory of thymic involution

Regression of the thymus is a key feature of immunosenescence, which coincides with a decrease in T cell output and contributes to the restriction of the T cell repertoire in the elderly, leading to increased susceptibility to illness and disease. However, the mechanisms involved in thymic involution are still not fully known. Although, it is often believed that thymic involution occurs during the onset of puberty, increasing data suggests alterations to the thymus happen much earlier in life. Therefore, the changes in the thymus and subsequent thymic function may not just be an ageing phenomenon. In this article, we propose that there are several, non-linear, phases to thymic atrophy, which are regulated by different mechanisms, including the familiar age-dependent thymic involution and a much earlier growth-dependent thymic involution.