Phonosurgery
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
A knowledge of the anatomy of the larynx, specifically the microarchitecture of the vocal folds is essential ( Figure 67.1 ). The layered structure of the vocal fold and the different mechanical and physical properties of each layer allow for the unique capacity for continuous vibration (or entrained oscillations). While the true mechanics of vocal fold vibration is still beyond our full understanding and requires active investigation, it is critical that this unique microarchitecture is preserved as its loss (i.e. vocal fold scar) results in the dramatic loss of voice quality. Vocal fold epithelium is the first identified layer of the vocal fold. The mucosa is comprised of stratified squamous epithelium, which transitions to pseudocolumnar cells superiorly into the laryngeal ventricle and inferiorly when the glottis transitions to the subglottis and trachea. The epithelium thickness is approximately 50 microns. The limited depth of the epithelium prevents physical manipulation of this layer alone. Surgical interventions designed to excise, or lift, the epithelium therefore requires some level of manipulation of the lamina propria. The specific layering of the human lamina propria is unique amongst mammalian species. The lamina propria is divided into three components: superficial, intermediate and deep. The main component of the lamina propria is collagen fibres. The composition of collagen fibre type and the fibre density distinguishes the three layers of the human vocal fold, which transitions from less-to-more dense structure extending from the superficial to deep. Depth of the superficial lamina is 0.14 mm in women and 0.30 mm in men. The vocal ligament is typically defined as the combined structure of the intermediate and deep layers of the lamina propria, which is readily identified histologically as well as microsurgically.
Introduction
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
The mucosa, or inner lining of the tract, is a mucous membrane (as are the other surfaces of externally communicating body channels or orifices). It is composed of a layer of epithelium in direct contact with the contents of the tract, connective tissue, and a thin layer of smooth muscle (Russ and Pawlina, 2015). The epithelium in the mouth, pharynx, esophagus, and anal canal is mainly nonkeratinized stratified squamous epithelium that serves a protective function. Simple columnar epithelium, which functions in secretion and absorption, lines the stomach and intestines. Neighboring simple columnar epithelial cells are firmly sealed to each other by tight junctions that restrict leakage between the cells. The rate of renewal of GI tract epithelial cells is rapid (5 to 7 days.) Located among the absorptive epithelial cells are exocrine cells that secrete mucus and fluid into the lumen of the tract, and several types of endocrine cells, collectively called enteroendocrine cells, that secrete hormones into the bloodstream. The lamina propria is areolar connective tissue containing many blood and lymphatic vessels, which are the routes by which nutrients absorbed into the tract reach the other tissues of the body. This layer supports the epithelium and binds it to the muscularis mucosae. The lamina propria also contains the majority of the cells of the mucosa-associated lymphatic tissue (MALT). These prominent lymphatic nodules contain immune system cells that protect against disease. MALT is present all along the GI tract, especially in the tonsils, small intestine appendix, and large intestine, and it contains about as many immune cells as are present in all the rest of the body. The lymphocytes and macrophages in MALT mount immune responses against microbes, such as bacteria, that may penetrate the epithelium. It should be noted that current ICH and FDA guidance suggests examination of the MALT tissues when evaluating potential immunotoxicity (Gad, 2015). A thin layer of smooth muscle fibers called the muscularis mucosae throws the mucous membrane of the stomach and small intestine into many small folds, which increase the surface area for digestion and absorption. Movements of the muscularis mucosae ensure that all absorptive cells are fully exposed to the contents of the gastrointestinal tract.
Gastrointestinal Tract
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Newborn animals seem to have no or minimal DALT at birth, but just as with MALT, DALT develops as animals mature and are exposed to environmental factors and bacteria. Secretory ducts of minor salivary glands are associated with follicles or lymphoid nodules, whereas plasma cells are interacinar. In mature animals, DALT is part of the integrated immune system of the GI tract, contributing to the secretory immunoglobulin-mediated immunity of the oral cavity. The intestine (in simplistic terms) contains the gut-associated lymphoid tissue (GALT), which is organized into Peyer’s patches in the antimesenteric aspect of the small intestine and lymphoid nodules in the cecum and colon. Components of GALT are not easily recognized grossly in large animals, but often appear as light gray serosal nodules in mice. Additionally, upon careful inspection of the intestinal mucosa, oval structures aligned along the long axis of the gut may be recognized on mucosal surfaces, especially in dogs. Caudal segments of the small intestine contain a larger number of Peyer’s patches than the proximal ones, but Peyer’s patches are present in all segments of the small intestine. Peyer’s patches are formed in the lamina propria extending into the submucosa by multiple domes that somewhat protrude into the gut lumen and are covered by follicle-associated epithelium, which contain M cells that serve as antigen-presenting cells (Figure 11.7b). Luminal contents are also sampled by antigen-presenting dendritic cells as their cell processes extend between epithelial cells. Additional components of the lymphoid system include intraepithelial lymphocytes that are mostly CD8 and CD4 cells in the lamina propria. The lamina propria also contains macrophages, plasma cells, mast cells, eosinophils, and regulatory T cells and other T lymphocytes. Furthermore, the intestinal defense mechanism contains proinflammatory components composed of cell membrane-associated toll-like receptors (TLRs) and cytosolic nucleotide-binding oligomerization domain molecules (Nod). Different TLRs and Nods recognize different components of bacteria and viruses and, in some way, are also able to distinguish pathogens from commensal organisms. In an interesting symbiosis, normal intestinal flora assures cytoprotection by inducing certain types of heat shock proteins to be produced by epithelial cells (MacDonald and Monteleone 2005). This anti-inflammatory function is confirmed by the observation that mice deficient in TLR signaling do not express Hsp25 and Hsp72 in their colonic epithelium and have greater sensitivity to dextran sulfate-induced colitis than wild-type mice, suggesting that normal flora may be protective against nonspecific damage through intact TLR signaling of the host. Much of the dome of the Peyer’s patch is taken up by B lymphocytes organized into follicles, whereas interfollicular regions are populated by T cells. Once B and T cells are activated in the Peyer’s patch, they migrate to the blood. Immune cells enter the lamina propria via a homing function that is achieved by high endothelial cell-lined postcapillary venules (HEVs). A unique feature of gut immunity is that circulating lymphocytes that were primed in the gut may populate other mucosal sites such as the respiratory or genital tract. Hence, there is a unified mucosal immune system wherever the host may be exposed to environmental stimulus. The colonic GALT is organized similarly, except it contains lymphoglandular structures that are formed by invaginations of the surface epithelium.
Vascular Changes in Eosinophilic Esophagitis (EOE), Report of an Unusual Case
Published in Fetal and Pediatric Pathology, 2020
Fatemeh Elham Mahjoub, Gholam Hossein Fallahi, Nakisa Niknejad
Background: Submucosal or lamina propria arteries are not often included in esophageal biopsies. We report an esophageal biopsy with eosinophilic esophagitis (EOE) overlying small arteries with medial hypertrophy to the point of obstruction. Case presentation: A two-year-old boy with a 1-year history of asthma frequently vomited after coughing. Esophageal biopsy showed EOE. Within the lamina propria there were small arteries with markedly thickened media to the point of luminal obstruction next to a hyperplastic lymphoid aggregate. There was no significant inflammatory infiltrate in the arterial walls. Subsequent biopsies did not show these vascular changes. Conclusion: Small artery changes in EOE have not previously been reported, and although the significance is unknown, in this case may be incidental to eosinophilic esophagitis.
Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis
Published in Tissue Barriers, 2020
Alistair Taverner, Julia MacKay, Floriane Laurent, Tom Hunter, Keyi Liu, Khushdeep Mangat, Lisa Song, Elbert Seto, Sally Postlethwaite, Aatif Alam, Apurva Chandalia, Minji Seung, Mazi Saberi, Weijun Feng, Randall J. Mrsny
Cholix (Chx) is expressed by the intestinal pathogen Vibrio cholerae as a single chain of 634 amino acids (~70.7 kDa protein) that folds into three distinct domains, with elements of the second and third domains being involved in accessing the cytoplasm of nonpolarized cells and inciting cell death via ADP-ribosylation of elongation factor 2, respectively. In order to reach nonpolarized cells within the intestinal lamina propria, however, Chx must cross the polarized epithelial barrier in an intact form. Here, we provide in vitro and in vivo demonstrations that a nontoxic Chx transports across intestinal epithelium via a vesicular trafficking pathway that rapidly achieves vesicular apical to basal (A→B) transcytosis and avoids routing to lysosomes. Specifically, Chx traffics in apical endocytic Rab7+ vesicles and in basal exocytic Rab11+ vesicles with a transition between these domains occurring in the ER-Golgi intermediate compartment (ERGIC) through interactions with the lectin mannose-binding protein 1 (LMAN1) protein that undergoes an intracellular re-distribution that coincides with the re-organization of COPI+ and COPII+ vesicular structures. Truncation studies demonstrated that domain I of Chx alone was sufficient to efficiently complete A→B transcytosis and capable of ferrying genetically conjoined human growth hormone (hGH). These studies provide evidence for a pathophysiological strategy where native Chx exotoxin secreted in the intestinal lumen by nonpandemic V. cholerae can reach nonpolarized cells within the lamina propria in an intact form by using a nondestructive pathway to cross in the intestinal epithelial that appears useful for oral delivery of biopharmaceuticals. One-Sentence Summary: Elements within the first domain of the Cholix exotoxin protein are essential and sufficient for the apical to basal transcytosis of this Vibrio cholerae-derived virulence factor across polarized intestinal epithelial cells.
Gut microbiota amplifies host-intrinsic conversion from the CD8 T cell lineage to CD4 T cells for induction of mucosal immune tolerance
Published in Gut Microbes, 2016
Jen Bon Lui, Lander S McGinn, Zhibin Chen
Microbiota has been shown to promote tolerogenic differentiation of T lymphocytes. It remains unclear to what extent microbiota triggers de novo re-programming or amplify pre-existing plasticity intrinsic to T cells. In a study with mouse models to track the clonal fate of CD4 and CD8 T cells, we discovered that CD8 T cells converted to MHC class I-restricted CD4 T cells without regard to selfness of their antigen specificity. In mesenteric lymph nodes (MLN), CD8 T cells converted to CD4+Foxp3+ regulatory T (Treg) cells which were enriched in the large intestine lamina propria (LILP) and suppressed chemical- or immune-mediated inflammatory damage. In germ-free conditions, the converted CD4 populations were present in MLN, but absent in LILP. Therefore, an intrinsic plasticity in the host was amplified by the gut microbiota, leading to selfless tolerance induction in the intestinal mucosa. The findings may be relevant to HIV infection, cancer and autoimmune disorders.