Appearance Of Goblet Cells Research Articles

VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway.

Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.

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

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 General Hospital, the clinical and pathological data of 453 patients who underwent gastroscopy and pathologically diagnosed with Barrett′s esophagus were retrospectively analyzed. The clinical pathological features were compared between patients with goblet cells and patients without goblet cells. Periodic acid Schiff reaction (PAS) staining was performed on pathological slides of Barrett′s esophagus with goblet cells, and the relationship between the number of goblet cells, the number of positive crypts of goblet cells and the severity of Barrett′s esophageal dysplasia was analyzed. T test and chi-square test were performed for statistical analysis. Results Among 453 patients with Barrett′s esophagus, 251 (55.4%) were males and 202 (44.6%) were females. There were 218 Barrett′s esophagus with goblet cells, including 128 males (58.7%) and 90 females (41.3%). The average onset age was (60.6±11.9) years old, and the peak onset age was between 60 and 69 years old. The appearance under endoscopy mainly was circumferential type (58.2%, 127/218). There were 235 Barrett′s esophagus without goblet cells, 123 males (52.3%) and 112 females (47.7%). The average onset age was (56.1±14.4) years old, and the peak onset age was between 50 and 59 years old. The appearance under endoscopy was mainly circumferential type (40.0%, 94/235). The incidence of dysplasia in Barrett′s esophagus with goblet cells was higher than that without goblet cells (75.7%, 165/218 vs. 37.0%, 87/235), and the difference was statistically significant (χ2=68.501, P<0.01). PAS staining showed that goblet cells were stained purplish red. The number of goblet cells, total number of crypts, the number of positive crypts of goblet cells and the proportion of positive crypts of goblet cells of Barrett′s esophagus with mild dysplasia were all significantly higher than those of Barrett′s esophagus with moderate dysplasia (95.50±40.56 vs. 40.00±13.34, 21.00±8.31 vs. 11.83±2.92, 16.50±6.17 vs. 7.50±2.47 and 0.79±0.42 vs. 0.63±0.12, respectively), and the differences were statistically significant(t=-4.503, -3.605, -4.690 and -4.340, all P<0.01). Conclusion Barrett′s esophageal dysplasia may be related with appearance of goblet cells, and the decrease or disappearance of goblet cells may indicate the progression of Barrett′s esophagus. Key words: Barrett′s esophagus; Goblet cells; Dysplasia; Esophageal adenocarcinoma

Ontogenic development of the digestive tract in larval and juvenile Vimba bream, Vimba vimba.

In this study we examined the ontogenic development of the digestive tract of Vimba bream (Vimba vimba, Family: Cyprinidae) during the first 60days of life (hatching to 60 days after hatching [DAH]). Samples of developing Vimba bream were randomly selected at various stages of development: 1-8, 10, 15, 20, 25, 30, 40, 50, and 60 DAH. For the histological and histochemical studies on the development of the alimentary canal, tissue sections prepared from the sampled hatchlings were stained with hematoxylin-eosin and periodic acid-Schiff and observed under a light microscope. The histological structures of both the mouth and esophagus were fully developed at 5 and 7 DAH, respectively. Intestinal differentiation was observed at 2 DAH, while mucosal folds appeared on the intestinal bulb at 7 DAH. At 5DAH, with the appearance of goblet cells in the epithelium of the mouth, pharynx, and esophagus, the larvae showed secretion activity in these organs. At 6 DAH, secretion was observed in the intestine; at this stage of development, the surface of the gastrointestinal tract was covered in a neutral mucous-like layer of polysaccharide. The histological observations indicate that the early development of the digestive tract in Vimba vimba enables larvae to efficiently ingest and digest exogenous feed very quickly after hatching.

Histomorphological changes in digestive tract of golden mahseer (Tor putitora) during different developmental stages.

Histomorphological changes in digestive tract of golden mahseer (Tor putitora) were examined in larvae [starting from hatching to 45days post-hatching (dph)], fry, fingerling, and adult. Digestive tract appeared during hatching, on the dorsal side of yolk sac, as a straight tube with a narrow lumen. Mouth opening and appearance of liver and pancreas were observed at 2dph, and subsequently anal opening, appearance of goblet cells in esophagus, and posterior intestine were evident at 3dph. The remodeling of oral cavity in terms of epithelial stratification, appearance of taste buds, and goblet cells were observed in a window of 4-5dph. Intestinal folding was found to be initiated at 8dph. From 12 to 45dph, thickening of oral and esophageal mucosal/extramucosal layers, increase in intestinal folding, increases in the density of goblet cells in entire gut were observed. Within the same time window, other histological changes such as disappearance of vacuoles in liver, and abundance of zymogen granules in pancreas were also observed. Supranuclear vesicles in mid-to-posterior intestine were found to be prominent from first feeding to 45dph; however, this phenomenon was no longer evident in fry and fingerling. Overall, the increase in intestinal folding and complexity of extramucosal layer were found to be continuous from the first appearance to adult, and this inferred the fact that the nutritional physiology, in terms of digestion and assimilation, progressively changes throughout the life stages of golden mahseer. Findings of this study will, therefore, help in preparing diets for different life stages of this fish, and in addition, the present information widens the understanding of digestive physiology of golden mahseer.

Towards High Speed Imaging of Cellular Structures in Rat Colon Using Micro-Optical Coherence Tomography

The mucosal microanatomy of the large intestine is characterized by the presence of crypts of Lieberkühn, which is associated predominantly with goblet cells. Such cellular-level intestinal microstructures undergo morphological changes during the progression of bowel diseases, such as colon cancer or ulcerative colitis. As an indicator of gastric cancers, intestinal metaplasia in the large intestine is characterized by the appearance of goblet cells in gastric epithelium, and therefore, visualization of intestinal microstructure changes in cross-sectional view, particularly in vivo, in a high-speed fashion would assist early disease diagnosis and its treatment. In this paper, we investigated the capability of micro-optical coherence tomography (μOCT) for high-speed cellular-level crypt and goblet cell structures imaging ex vivo and in vivo . The adopted μOCT system achieved a resolution of 2.0 μm in both the lateral and axial directions in air. Ex vivo and video-rate in vivo images acquired in 3-D at respective imaging rates of 20 and 60 frames/s are presented and compared with the histology images. Imaging results show that the detailed microstructures, such as the crypt lumen and the goblet cells, could be clearly identified and are also comparable with those in histology images. Such comparisons also indicate that high-resolution μOCT could be a powerful tool to perform “optical biopsy” in colorectal tissue. This is the first work, to the best of our knowledge, on cellular-level structure imaging in intestinal mucosa using spectral-domain OCT.

Imaging of goblet cells as a marker for intestinal metaplasia of the stomach by one-photon and two-photon fluorescence endomicroscopy

Goblet cells are a requirement for the diagnosis of intestinal metaplasia of the stomach. The gastric mucosa is lined by a monolayer of columnar epithelium with some specialization at the crypts, but there are no goblet cells in normal gastric epithelium. The appearance of goblet cells in gastric epithelium is an indicator of potential malignant progression toward adenocarcinoma. Therefore, in vivo three-dimensional imaging of goblet cells is essential for diagnoses of a premalignant stage of gastric cancers called intestinal metaplasia. We used mouse intestine, which has goblet cells, as a model of intestinal metaplasia. One-photon confocal fluorescence endomicroscopy and two-photon fluorescence endomicroscopy are employed for 3-D imaging of goblet cells. The penetration depth, the sectioning ability, and the photobleaching information of imaging are demonstrated. Both endomicroscopy techniques can three-dimensionally observe goblet cells in mouse large intestine and achieve an imaging depth of 176 microm. The two-photon fluorescence endomicroscopy shows higher resolution and contrast of the imaging sections at each depth. In addition, two-photon fluorescence endomicroscopy also has advantages of sectioning ability and less photobleaching. These results prove that two-photon fluorescence endomicroscopy is advantageous in diagnoses of a premalignant stage of gastric cancers.

Identification of Epithelial Gaps in Human Small and Large Intestine by Confocal Endomicroscopy

Confocal endomicroscopy is an emerging technology that poses the endoscopist with challenges for identifying epithelial structures in the human intestine. We have shown previously that the murine intestinal epithelium is punctuated by gaps caused by cell shedding. The goals of this study were to determine if confocal endomicroscopy could resolve the presence of human epithelial gaps and whether a proinflammatory cytokine could increase cell shedding. Intestinal mucosa was imaged after staining with acriflavine. Confocal endomicroscopy of 17 patients yielded 6277 images from the human terminal ileum and rectum. Results were validated by parallel studies of anesthetized mice (wild-type and Math1(DeltaIntestine)) using rigid confocal probe microscopy, 2-photon/confocal microscopy, and scanning electron microscopy. Human terminal ileal and rectal epithelium revealed unstained areas with the diameter of an individual epithelial cell, with 2 distinct morphologies. One had a "target" appearance, shown by mouse studies to be goblet cells. The other morphology had no nucleus and was observed by rigid confocal probe microscopy and scanning electron microscopy in the villi of Math1(DeltaIntestine) mice, which lack goblet cells. In the mouse, tumor necrosis factor alpha (0.33 microg/g intraperitoneally) increases cell shedding by 27-fold and caused loss of barrier function across 20% of resultant gaps. Confocal endomicroscopy can distinguish between epithelial discontinuities (gaps) and goblet cells in human intestine. Results suggest that the sealing of epithelial gaps must be considered as a component of the intestinal barrier and has potential implications for intestinal barrier dysfunction in human disease.

Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett’s esophagus and esophageal adenocarcinoma

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.

Endoscopic surveillance of columnar-lined esophagus: frequency of intestinal metaplasia detection and impact of antireflux surgery: Oberg S, Johansson J, Wenner J, et al., Barrett’s Esophagus: Surgeons to the Rescue? Ann Surg, 2001;234:619–26

The aim of this study was to evaluate the prevalence of intestinal metaplasia (IM) in patients with varying lengths of columnar-lined esophagus (CLE) during long-term surveillance. Further, the authors hoped to determine whether complete reflux prevention by medical or surgery therapy prevented the development of IM in CLE. Between the year 1979 and 1998, the authors prospectively enrolled patients with CLE into a surveillance program that included endoscopy every 1–2 yr. The majority of the patients were biopsied in a systematic fashion (four quadrant biopsies, every 2 cm). Patients without IM on the two initial endoscopies were deemed Barrett’s free. The time separating the negative endoscopies and the appearance of goblet cells on subsequent endoscopies was identified as the time to metaplasia. The time to this occurrence was compared between patients with medically and surgically treated reflux. A total of 177 patients were enrolled, and 52% had IM on initial endoscopy. At the first endoscopy, 30% of patients with CLE 1–2 cm in length had IM. This was compared with 45% of patients with CLE 3–4 cm in length. After six endoscopies, the yield increased to 64% of patients with CLE 1–2 cm in length and 89% of patients with CLE 3–4 cm in length. Overall, patients with longer CLE (>4 cm) had IM discovered with fewer endoscopies than those with shorter CLE. A total of 69 patients had no IM on the initial two endoscopies. In this retrospective analysis, 49 had been treated with antireflux medication, and 20 were treated with surgery. Post-surgery pH studies showed that 48 of 49 patients had normal esophageal acid exposure. Esophageal pH studies were not reported for medically treated patients. The time to development of IM was shorter in medically treated patients (mean time 5.3 yr). Overall, 35 of 69 patients had IM on follow-up biopsies. Using a multivariant analysis, surgically treated reflux decreased the risk of development of IM by 10-fold.

New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis

PurposeTo introduce a new surgical procedure for treating superior limbic keratoconjunctivitis (SLK) and to suggest the association of SLK with conjunctivochalasis. DesignInterventional case series. MethodsSix eyes of five patients with long-standing severe ocular irritation unresponsive to treatment with topical steroid and artificial tears were operated on using our new procedure. This technique consists of four steps as follows: (1) Rose bengal (RB) staining is used to localize the abnormal conjunctival area; (2) an arc-like conjunctival incision is placed from the 2 to the 10 o’clock position adjacent and distal to the RB-stained area; (3) the conjunctiva is resected to form a crescent using the arc-like incision as the base; the size of the resection is determined by conjunctival redundancy after removal of the subconjunctival connective tissue; and (4) the crescent conjunctival opening is closed with interrupted sutures. In two eyes, the new surgical procedure was performed together with surgery for inferior bulbar conjunctivochalasis. ResultsIn all operated eyes, RB staining had disappeared by the end of the second postoperative week; recovery from symptoms and loss of inflammation were recorded by 1 month after treatment. In the case with the longest follow-up (14 months), there was cytologic evidence of goblet cell recovery at 3 months after the operation. In another, there was normalization of the nucleo/cytoplasmic ratio of conjunctival cells without the appearance of goblet cells. ConclusionsOur treatment very effectively resolved symptoms associated with SLK, even in eyes unresponsive to conventional therapy with eye drops. Considering that we did not address the diseased part of the conjunctiva but rather the adjacent conjunctival redundancy, we propose that superior bulbar conjunctivochalasis is involved in the pathogenesis of SLK.

VEGF-dependent conjunctivalization of the corneal surface.

To investigate the mechanisms governing corneal neovascularization and the appearance of goblet cells in a murine model of limbal insufficiency. The spatial and time-dependent relationship between corneal neovascularization and goblet cell density was analyzed in corneal flatmounts. Immunohistochemical detection of the vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR1) was performed in paraffin-embedded sections. A transgenic mouse that expresses the reporter gene lacZ targeted to the Flt-1 locus through homologous recombination was used to analyze corneal expression of Flt-1. The presence of soluble and membranous goblet cell Flt-1 mRNA and protein content was assessed with Northern and Western blot analyses, respectively. Finally, systemic adenoviral expression of a soluble Flt-1/Fc construct was used to study the effect of inhibition of VEGF bioactivity on the appearance of goblet cells and neovascularization. Corneal neovascularization preceded the appearance of goblet cells, although both processes overlapped temporally. Flt-1 was abundant in the conjunctiva-like epithelium covering the cornea, as well as in the goblet cells, invading leukocytes, and vasculature. A similar expression pattern was observed in the transgenic mice expressing the lacZ gene downstream from the Flt-1 promoter. Isolated human and rat goblet cells in culture expressed Flt-1 mRNA and protein, as did freshly isolated human conjunctiva. The systemic inhibition of VEGF bioactivity potently suppressed both corneal neovascularization (8.3% +/- 8.1% vs. 41.1% +/- 15.3% corneal area; P < 0.001) and corneal goblet cell density (1.6% +/- 2.5% vs. 12.2% +/- 2.4% corneal area; P < 0.001). Two important features of corneal conjunctivalization, the appearance of goblet cells and neovascularization, are regulated by VEGF. Both processes are probably mediated, in part, through the Flt-1 receptor. Taken together, these data indicate that an anti-VEGF therapeutic approach may limit the visual loss associated with conjunctivalization of the corneal surface.

Prevalence of mAbDAS-1 positivity in biopsy specimens from the esophagogastric junction

OBJECTIVE: Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. METHODS: In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. RESULTS: mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. CONCLUSIONS: In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.

Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction.

Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.

Limbal stem cells in health and disease.

Stem cells are present in all self-reviewing tissues and have unique properties. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. These epithelia are stratified, squamous and non-keratinized. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. The stem cells for the cornea are located at the limbus. The microenvironment of the limbus is considered to be important in maintaining stemness of the stem cells. They also act as a "barrier" to conjunctival epithelial cells and prevent them from migrating on to the corneal surface. In certain pathologic conditions, however, the limbal stem cells may be destroyed partially or completely resulting in varying degrees of stem cell deficiency with its characteristic clinical features. These include "conjunctivalization" of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. The stem cell deficiency can be managed with auto or allotransplantation of these cells. With the latter option, systemic immunosuppression is required. The stem cells can be expanded ex vivo on a processed human amniotic membrane and transplanted back to ocular surface with stem cell deficiency without the need of immunosuppression.

Limbal Stem Cells of the Corneal Epithelium

Stem cells have certain unique characteristics, which include longevity, high capacity of self-renewal with a long cell cycle time and a short S-phase duration, increased potential for error-free proliferation, and poor differentiation. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. Stem cells for the cornea reside at the corneoscleral limbus. The limbal palisades of Vogt and the interpalisade rete ridges are believed to be repositories of stem cells. The microenvironment of the limbus is considered to be important in maintaining the stemness of stem cells. Limbal stem cells also act as a “barrier” to conjunctival epithelial cells and normally prevent them from migrating on to the corneal surface. Under certain conditions, however, the limbal stem cells may be partially or totally depleted, resulting in varying degrees of stem cell deficiency with resulting abnormalities in the corneal surface. Such deficiency of limbal stem cells leads to “conjunctivalization” of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. This results in ocular discomfort and reduced vision. Partial stem cell deficiency can be managed by removing the abnormal epithelium and allowing the denuded cornea, especially the visual axis, to resurface with cells derived from the remaining intact limbal epithelium. In total stem cell deficiency, autologous limbus from the opposite normal eye or homologous limbus from living related or cadaveric donors can be transplanted on to the affected eye. With the latter option, systemic immunosuppression is required. Amniotic membrane transplantation is a useful adjunct to the above procedures in some instances.

Histologic and Histochemical Studies on the Lamina Epithelialis of the Oesophagus of the Carp (Cyprinus carpio L.)

In this investigation, it was aimed to examine histological and histochemical peculiarities of Lamina epithelialis at Carp (Cyprinus carpio) oesophagus. As a material, 12 oesophagus were used. Lamina epithelialis which showed pseudostratified epithelia at the short posterior region of oesophagus before the intestine while other parts showed stratified squamous epithelium and taste buds were not established. It was determined that the mucous secreting cells at the epithelium of anterior and median region of oesophagus formed a highly wide layer. The secretory material of these cells were found to be a mixture of neutral and acidic mucosubstance. Also mucous secreting cells in the posterior region showed same histochemical characters and they were identified to have a typical appearance of goblet cells. The other cells of L. epithelialis no gave reaction with histochemical dye methods.

Changes in Lectin-Binding Patterns during Late Fetal Development of the Rat Colon

Lectin-binding and histochemical studies were integrated with a morphological description of colon development in rat fetuses to determine whether changes in glycoprotein sugars could be identified with stages of colon organogenesis. At 16 days gestation the colon consisted of a minute lumen surrounded by 3-5 layers of cuboidal, stratified epithelium, a basement membrane and undifferentiated mesenchyme. As development proceeded, epithelial spaces eventually fused with the main lumen, and fingers of mesenchyme, with a basement membrane and epithelial mantle, formed the walls of crypts lined with simple to stratified columnar cells. Goblet cells and mucin production appeared only on the 20th-21st day of gestation. Mesenchyme differentiation to a circular muscle band, the prospective tunica muscularis, occurred on days 17-18, and vascularization of the lamina propria was first detected on day 19. Wheat germ agglutinin (WGA) lectin bound avidly to sugar residues in the mesenchyme matrix from day 16 but weakened as the tissue differentiated, particularly into smooth muscle. Alcian blue staining of the matrix, also weakening with time, confirmed the sialic acid nature of binding sites for WGA on matrix acid mucopolysaccharides. Under controlled conditions, WGA also detected N-acetylglucosamine-binding sites on brush borders as they developed on the apical surface of primitive enterocytes. Ulex lectin bound to fucose residues of Alcian-blue-positive, PAS-positive mucin from the first appearance of goblet cells. Concanavalin A and glycine max lectins bound only to blood group substances on both nucleated red cells between days 16 and 19 and anucleate red cells from day 19.(ABSTRACT TRUNCATED AT 250 WORDS)

An Experimental Study of Bronchial Glands

Patients with primary idiopathic obstructive pulmonary emphysema who had the reduction in lung volume and the bilateral bronchopulmonary denervation operation revealed marked atrophy of submucosal bronchial glands when compared with the normal and with the unoperated patient with pulmonary emphysema. In addition, there was considerable reduction of PAS positive secretions and an absence of secretion stained by Alcian blue, thus indicating less neutral mucopolysaccharides and an absence of acid mucopolysaccharides. There was also atrophy of submucosal layers of the bronchi. The submucosal bronchial glands of the domestic pig with the bronchopulmonary denervation operation showed marked atrophy when compared with normal control animals. There was a decrease in PAS positive secretions and a marked decrease in Alcian blue staining secretions from these atrophied glands. There was an appearance of goblet cells in the bronchial mucosa after bilateral bronchopulmonary denervation not found in normal control pigs without denervation. In addition, there was marked atrophy of the submucosal and mucosal layers of the bronchi after bilateral bronchopulmonary denervation.