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Cell production in mouse intestinal epithelium measured by stathmokinetic flow cytometry and Coulter particle counting.

The rate of cell production in the crypt population of the intestinal epithelium has been determined previously. However, the complex geometry of the tissue makes determination of the rate of cell production in the epithelium as a whole, by traditional methods, extremely difficult if not impossible. In this report, stathmokinetic flow cytometry was used for the direct determination of the rate of cell production in the mouse intestinal epithelium. Mice were given an intraperitoneal injection of colcemid (2.5 mg/kg) and killed 25, 45, 65 and 90 min after injection. The percentage of cells with 4N DNA (G2 and M phase cells) in the epithelium at each time interval was determined with flow cytometry. The results were fitted by linear regression and the rate of cell production derived from the slope of the regression line. Thus, the rate of cell production was found to be 1.86% +/- 0.44 (means +/- SE) per hour in the jejunal epithelium and 1.66% +/- 0.48 per hour in the colonic epithelium. The turnover time of the epithelium as a whole was determined from the inverse of the rate of cell production, and was found to be 53.8 h +/- 12.6 in jejunum and 60.2 h +/- 17.3 in colon. Coulter particle counting was used to measure the number of cells in the intestinal epithelium. The number of epithelial cells was found to be 1.90 X 10(7) +/- 3.11 X 10(5) cells per cm2 in the jejunum and 8.98 X 10(6) +/- 8.05 X 10(5) cells per cm2 in the colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Induction of alveolar type II cell differentiation in fetal tracheal epithelium by grafted distal lung mesenchyme.

Normal branching morphogenesis and cytodifferention of the lung require a specific interaction between the epithelial rudiment and pulmonary mesenchyme. Previous studies in the mouse have shown glandular stage pulmonary mesenchyme can elicit a lung-like pattern of branching morphogenesis when grafted onto tracheal epithelium of the same age that has been denuded of its own mesenchyme. We have examined whether are not this pattern of branching is accompanied by changes in epithelial cytodifferentiation. Purified pulmonary mesenchyme was isolated from the distal tips of day 13-14 fetal rat lungs and grafted onto a stretch of tracheal epithelium from which the mesenchyme had been removed. The grafts were cultured on semisolid 0.5% agarose in Waymouth's medium containing 10% serum for 5 days and then for an additional 2 days in the same medium containing 10(-6) M cortisol. Unoperated or operated-ungrafted tracheae and intact lung explants served as controls. Grafting distal tip pulmonary mesenchyme onto the tracheal epithelium induced a pattern of branching identical to that seen in control lung explant cultures, while ungrafted control tracheal cultures formed cystic structures. Light microscopy of the induced tracheal epithelium showed that the constituent cells exhibited a morphology virtually identical to cells in control lung explants. Ultrastructural analysis demonstrated that the induced tracheal epithelial cells contained lamellar inclusion bodies, and the lumina of the induced acinar structures contained tubular myelin figures. Reverse transcription polymerase chain reaction analysis of the induced tracheae revealed the presence of mRNAs for surfactant protein A (SP-A) and SP-B, as well as SP-C, which is a specific marker for type II cell differentiation in the adult rat. Control tracheal cultures contained mRNAs only for SP-A and SP-B. Immunocytochemistry demonstrated that many cells within the induced tracheal epithelium were positive for SP-A and SP-C proteins. Further studies demonstrated that the ability of mesenchyme to induce tracheal epithelium varied within the pulmonary tree, and that the competence of the tracheal epithelium to respond to the influence of distal tip mesenchyme was temporally restricted. Our results demonstrate that pulmonary mesenchyme can act instructively on the tracheal epithelium to induce a program of type II cell differentiation.

Animals↗

Genetic alterations in normal epithelium of colorectal cancer patients may be a useful indicator for subsequent metachronous tumor development.

BACKGROUND: We attempted to identify areas of microsatellite alterations specific to histologically normal colorectal epithelium and to clarify the correlations among those molecular events and clinicopathologic features. METHODS: We conducted a prospective observation study on 51 colorectal cancer patients. Preoperative blood and microdissected histologically normal colorectal epithelium and neoplastic tissues were collected. Microsatellite analyses with seven microsatellite loci were performed to examine the genetic potential of individual tumors and histologically normal colorectal epithelium. RESULTS: In the sporadic colorectal cancer group, p53 LOH in the neoplastic epithelium had a significant correlation with the maximum tumor diameter and the preoperative serum cancer antigen 19-9 level, but not with the depth of invasion of the primary tumor. Among the patients who had p53 LOH in the histologically normal colorectal epithelium, four additional tumors were discovered within 30 months after curative surgery. For those patients, microsatellite alterations in normal colorectal epithelium were more sensitive than tumor markers. CONCLUSIONS: For accurate LOH analysis, nonmalignant lymphocytes from blood should be used as the appropriate normal DNA sample. Focusing on the identification of high-risk patients for microsatellite alterations in histologically normal colorectal epithelium can be a useful indicator of subsequent metachronous tumor development after colorectal surgery. For accurate LOH analysis, nonmalignant lymphocytes from blood should be used as the appropriate normal DNA sample. Focusing on the identification of high-risk patients for microsatellite alterations in histologically normal colorectal epithelium can be a useful indicator of subsequent metachronous tumor development after colorectal surgery.

Biomarkers, Tumor↗

An immunohistochemical and monastral blue-vascular labelling study on the involvement of capsaicin-sensitive sensory innervation of the junctional epithelium in neurogenic plasma extravasation in the rat gingiva.

Nerve fibres immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP) were located preferentially at the base of the junctional epithelium. Occasional fibres were observed in close proximity to the subepithelial, small blood vessels. The vascular connective tissue papillae projecting into the epithelium were more densely surrounded by SP- and CGRP-immunoreactive fibres in the interdental col than in other regions of the gingiva. In some cases, hyperplasia of the junctional epithelium was noted in the interdental col where the connective tissue papillae were invaded by widened vessels, indicating severe irritation. SP- and CGRP-immunoreactive fibres around these papillae showed increases in their immunoreactivity and thickness, with some fibres terminating as large expansions. Double immunohistochemical staining revealed the co-existence of SP and CGRP in all nerve fibres within and under the junctional epithelium. Capsaicin pretreatment eliminated most of the immunoreactivity for both peptides. Intravenous infusion of capsaicin or SP caused increased permeability in vessels underlying the junctional epithelium, as indicated by Monastral blue labelling. Labelled vessels were arranged not only in a network extending under the epithelium but also in loops protruding into the connective tissue papillae. These labelled vessels were most abundant in the interdental col, where vascular loops with more complex configurations exhibited strong staining in their walls. In the case of hyperplasia of the junctional epithelium in the interdental col, widened vessels showing extensive labelling in their walls were observed. In capsaicin-pretreated animals, capsaicin-induced extravasation was abolished, while the effect of SP was still observed. These findings provide evidence that capsaicin-sensitive sensory nerves supplying the junctional epithelium are involved in neurogenic plasma extravasation in the rat gingiva. The enhancement of neurogenic plasma extravasation in the col may be vascular response associated with a higher susceptibility of this region to gingival inflammation.

Animals↗

Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced.

In this review, we define the two major tissue types, epithelium and mesenchyme, and we describe the transformations (transdifferentiations) of epithelium to mesenchyme (EMT) and mesenchyme to epithelium (MET) that occur during embryonic development. The differentiation of the metanephric blastema provides a striking example of MET. Differentiation of metanephric epithelium is promoted by matrix molecules and receptors (nidogen, laminins, alpha 6 integrins), hepatic growth factor/scatter factor, and products of the genes wnt-1, wnt-4, and Pax-2. Transformation of MDCK epithelium to mesenchyme-like cells is promoted in vitro by antibodies to E-cadherin, products of v-src, v-ras, and v-mos, and by manipulation of the epithelium on collagen gels. Suspension in collagen gel, transforming growth factors, and c-fos have also been shown to promote EMT in epithelia. We present studies from our laboratory showing that alpha 5 beta 1 integrin has a role in the EMT of lens epithelium that is brought about by suspension in collagen gel. Our laboratory has also shown that transfection with the E-cadherin gene induces embryonic corneal fibroblasts to undergo MET and that this MET is enhanced by interaction of the differentiating epithelium with living fibroblasts. This review calls attention to the roles that EMT and MET might have in kidney pathologies and urges further study of the involvement of these phenomena in renal development, renal injury, and renal malignancy.

Animals↗

In vitro inhibition of androstenedione 5alpha-reduction by finasteride in epithelium and stroma of human benign prostatic hyperplasia.

Finasteride is a well known steroid 5alpha-reductase inhibitor. In this context, recently we have shown that in human benign prostatic hyperplasia (BPH) finasteride inhibits the 5alpha-reduction of testosterone to dihydrostestosterone (DHT) more effectively in the epithelium as compared to the stroma. The aim of the present study was to describe in epithelium and stroma of human BPH the effect of finasteride on the 5alpha-reduction of androstenedione, that is the second main circulating androgen in men, to androstanedione. Using a finasteride concentration of 75 nM and an androstenedione concentration of 220 nM, the mean inhibition [% +/- SEM] of 5alpha-reductase activity was significantly higher in epithelium (69 +/- 2) than in stroma (52 +/- 4). Both in epithelium and stroma, this inhibition of 5alpha-reductase activity was dose-dependent and competitive. Dixon plots as well as slope replots of Lineweaver-Burk plots showed that the mean inhibition constant Ki (nM +/- SEM) was significantly lower in epithelium (10 +/- 1 and 11 +/- 2, respectively) than in stroma (33 +/- 7 and 28 +/- 4, respectively) indicating a significantly stronger inhibitory effect of finasteride in epithelium. From those mean Ki values, it follows that in human BPH finasteride inhibits equally well both the 5alpha-reduction of androstenedione to androstanedione and testosterone to DHT. Based on these inhibition studies, there is no evidence for the coexistence of substrate-specific 5alpha-reductases converting either testosterone or androstenedione. However, the striking difference in finasteride sensitivity of the 5alpha-reduction between epithelium and stroma could be due to a cell-type specific expression of structurally different 5alpha-reductases as well as to a different access of finasteride to 5alpha-reductase in epithelium and stroma where, compared to each other, the lipid environment is significantly different.

Aged↗

Plunc, a member of the secretory gland protein family, is up-regulated in nasal respiratory epithelium after olfactory bulbectomy.

Subtraction suppression hybridization was used with high throughput screening to identify transcripts of genes that are differentially expressed in nasal epithelium following lesioning of the olfactory bulb, termed bulbectomy. We isolated the rat homologue of plunc, a murine gene highly expressed in lung and nasopharyngeal regions, by this method. Rat plunc encodes a 270-amino acid protein containing a putative signal peptide. plunc up-regulation in respiratory epithelium was confirmed by Northern blot and in situ hybridization. plunc mRNA was expressed in nasal epithelium, heart, lung, thymus, and salivary gland in adult rodent. plunc was expressed in nasal epithelium, thymus, and salivary gland during embryogenesis. Antibodies against Plunc detected a 31-kDa protein in lung, heart, and spleen. Rat nasal epithelium displayed robust immunoreactivity that was highly localized to the microvilli layer of respiratory epithelium. The expression of plunc was up-regulated after bulbectomy in respiratory epithelium. We also detected secreted plunc in rat and human mucus. Sequence and homology analyses suggest that Plunc is a member of the secretory gland protein family with putative bactericidal/bacteriostatic function. This is the first protein found in respiratory epithelium whose expression is regulated by olfactory neuronal injury and may provide protection against infection subsequent to injury.

Amino Acid Sequence↗

Metabolic competence and susceptibility of intestinal epithelium to genotoxic injury during regeneration.

The carcinogenic potency of many mutagens is increased in conditions of tissue regeneration. This involves fundamental changes of cellular division and differentiation, in intestinal epithelium. However, effects on epithelial capacity for carcinogen metabolism and susceptibility to genotoxic injury are unknown. Using a novel rat model, this study assessed expression of cytochrome P450 mono-oxygenases (Cyps), glutathione S-transferases (GSTs) and uridine diphosphoglucuronosyl transferase (UGT) in intestinal epithelium during sequential stages of regeneration. Enzyme induction and DNA adduct formation were also assessed after benzo[a]pyrene (BaP) exposure. Control assays were carried out in normal intestinal epithelium. Fewer phase I and II xenobiotic metabolizing enzymes were expressed in regenerating intestinal epithelium than in normal control intestinal epithelium (GSTA3, UGT in regeneration vs Cyp2B, GSTA1/2, GSTA4, GSTP1, UGT in control). Benzo[a]pyrene induced GSTA3 and UGT in regeneration vs Cyp1A, Cyp2B, GSTA1/2, GSTA3, GSTA4, GSTP1 and UGT in control normal intestinal epithelium. Benzo[a]pyrene induced low levels of GSTA3 in early regenerating intestinal epithelium but induction increased by >2-fold at late stage regeneration. Higher levels of benzo[a]pyrene 7,8-diol-9,10-epoxide (BPDE) DNA adducts were formed at early stages of regeneration, than at later stages. Intestinal epithelium displayed reduced metabolic competence and differential susceptibility to genotoxic injury from BaP, during regeneration.

Animals↗

Take percentage and conditions of cultured epithelium were improved when basement membrane of the graft was maintained and anchoring mesh was added.

To achieve a higher take rate for epithelial grafts, this study investigated grafting techniques. Seventy-seven nude mice received flap grafting in which cultured human epithelium was grafted inside the flap, and 55 nude rats received transplantation of epithelium to a full-thickness skin defect. In each group, four models were studied, including model 1, in which epithelium was cultured with the conventional method; model 2, in which epithelium was cultured with fibrin gel to avoid sheet damage, then absorptive mesh was incorporated into the epithelium for anchoring to the graft bed; model 3, in which epithelium was cultured with fibrin gel and combined with absorptive mesh and artificial dermis containing fibroblasts; and model 4, in which the model 2 epithelium was grafted after artificial dermis was transplanted. The take for these models was evaluated grossly and histologically. The results show that the take percentage of models 2 and 3 was significantly higher than that of model 1 (conventional epithelium) and that there was no significant difference between model 3 (simultaneous grafting) and model 4 (two-step grafting). The difference in the take percentages of the grafts to the flap and to the full-thickness skin defect was also insignificant. In immunohistochemistry, human keratin appeared in all epidermis layers and diversification of the layer was observed in models 2, 3, and 4. In these three models, type IV collagen appeared in the basal layer and the formation of basal membrane was confirmed. These findings suggest that epithelia cultured on fibrin gel and combined with absorptive mesh could be used in a new technique for better, more stable take.

Absorbable Implants↗

Low glutathione and glutathione S-transferase levels in Barrett's esophagus as compared to normal esophageal epithelium.

Patients with Barrett's esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class alpha, mu, pi, and theta isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett's esophagus were taken from both Barrett's and adjacent normal squamous epithelium. GST enzyme activity towards 1-chloro-2,4-dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon's signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35%, and GST mu, GST pi and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST alpha and GST theta levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett's epithelium may therefore contribute to the increased cancer risk in this tissue.

Adult↗

Gland ducts and multilayered epithelium in mucosal biopsies from gastroesophageal-junction region are useful in characterizing esophageal location.

SUMMARY. There is controversy as to whether oxynto-cardiac mucosa (OCM), cardiac mucosa (CM) and intestinal metaplasia (IM) found in the gastroesophageal-junction region line the anatomic stomach, esophagus or both. A total of 785 retroflex biopsies taken at the endoscopic gastroesophageal junction in 244 patients were evaluated for the presence of gland ducts and multilayered epithelium which are two recognized markers of esophageal mucosa. Oxyntic mucosa was found in 287 biopsies, OCM in 283, CM in 158, IM in 30 and squamous epithelium in 53 (some biopsies had more than one epithelial type). Esophageal gland ducts and multilayered epithelium were absent in all biopsies with oxyntic mucosa. Sixty-four (13.6%) of 471 biopsies with OCM, CM and IM contained esophageal gland ducts, and 68 of 471 (14.4%) contained multilayered epithelium. Ninety-eight of 471 (20.8%) biopsies contained either gland ducts or multilayered epithelium. This study shows that 20.8% of biopsies at the gastroesophageal junction with OCM, CM and IM can be definitively characterized as lining the anatomic esophagus by the finding of gland ducts and multilayered epithelium. The absence of these markers in oxyntic mucosa confirms this epithelium as gastric. The presence of gland ducts and multilayered epithelium can be used by pathologists to objectively ascribe an esophageal or gastric location to a biopsy from the gastroesophageal junction.

Biopsy↗

Multilayer culture of periodontal ligament epithelial cells: a model for junctional epithelium.

The unique features of junctional epithelium involve lack of keratinization, limited differentiation and a relatively permeable structure. In order to study the relationship between differentiation and permeability of stratified epithelium a model system was developed. Porcine periodontal ligament epithelial cells were cultured on the polycarbonate nucleopore membrane of the Transwell two-compartment culture system. Within 5 days of culture the cells formed a confluent multilayered structure. Subsequently, maturation of the structure and differentiation of surface cells took place. Transmission electron microscopy showed that the cells were arranged into basal and suprabasal layers with sparse desmosomal attachments and wide intercellular spaces resembling the organization of junctional epithelium. The basal cells attached to a subepithelial basal lamina through numerous hemidesmosomes. The cytokeratin profile of the cultured epithelium (K5, 6, 14, 16, 19) resembled that of the cells of junctional epithelium attached to the tooth surface. The older cultures expressed differentiation markers, K4, K13 and involucrin, thereby resembling sulcular epithelium. The epithelial permeability, measured by diffusion of phenol red, radioactive dextran or methionine tracers, and as transepithelial electrical resistance, decreased with the increased cell number and maturation of the cultures. The new model provides an organotypic culture system which allows to control differentiation of a multilayered periodontal epithelium. It thus may serve as a valuable new tool for studies on the permeability and behaviour of periodontal epithelium under the influence of exogenous and endogenous factors.

Analysis of Variance↗

Surgical procedures in the treatment of most severe eye burns. Revival of the artificial epithelium.

Report of some clinical observations in 16 patients with severe and most severe burns of 19 eyes. Major problems were delayed regeneration of the epithelium, extensive ulceration of the sclera near the limbus, and subsequent corneal ulceration. The therapy with anti-inflammatory drugs, macromolecular hyaluronic acid, fibronectin, epidermal growth factor, free transplants of oral mucosa and conjunctiva was sometimes helpful, but could not induce stable epithelial regeneration. The major problem remained the inability of the epithelium to regenerate on the cornea. Therefore, an artificial epithelium was applied in many cases. When healthy conjunctiva touched closely the artificial epithelium at the limbus, it remained tightly attached to the corneal stroma, preserved it's structure and even prevented corneal vascularisation for many months. However, when corneo-scleral ulceration was present, the artificial epithelium failed to protect the corneal stroma from secondary ulceration and sloughed off. Therefore, new surgical procedures, a conjunctiva-Tenon flap and a Tenon plasty were introduced to cover and to cure corneoscleral ulceration. These operations formed a new limbus, attached tightly to the rim of the artificial epithelium and prevented secondary ulceration underneath. Then under the protection of the artificial epithelium and the Tenon plasty the eye could be treated topically with corticosteroids for a long time. When the inflammatory response to the burn was healed, the natural epithelium recovered and the eye became ready for successful keratoplasty.

Burns, Chemical↗

Increased antigen and bacterial uptake in follicle associated epithelium induced by chronic psychological stress in rats.

BACKGROUND: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats. AIM: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake. SUBJECTS AND METHODS: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to (51)Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy. RESULTS: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface. CONCLUSIONS: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer's patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa.

Acute Disease↗

Nitric oxide synthase isoform expression in the developing lung epithelium.

Nitric oxide (NO), generated by NO synthase (NOS), is an important mediator of physiological processes in the airway and lung parenchyma, and there is evidence that the pulmonary expression of the endothelial isoform of NOS (eNOS) is developmentally regulated. The purpose of the present study was to delineate the cellular distribution of expression of eNOS in the developing respiratory epithelium and to compare it with inducible (iNOS) and neuronal (nNOS) NOS. Immunohistochemistry was performed on fetal (125-135 days gestation, term 144 days), newborn (2-4 wk), and maternal sheep lungs. In fetal lung, eNOS expression was evident in bronchial and proximal bronchiolar epithelia but was absent in terminal and respiratory bronchioles and alveolar epithelium. Similar to eNOS, iNOS was detected in bronchial and proximal bronchiolar epithelia but not in alveolar epithelium. However, iNOS was also detected in terminal and respiratory bronchioles. nNOS was found in epithelium at all levels including the alveolar wall. iNOS and nNOS were also detected in airway and vascular smooth muscle. The cellular distribution of all three isoforms was similar in fetal, newborn, and adult lungs. Findings in the epithelium were confirmed by isoform-specific reverse transcription-polymerase chain reaction assays and NADPH diaphorase histochemistry. Thus the three NOS isoforms are commonly expressed in proximal lung epithelium and are differentially expressed in distal lung epithelium. All three isoforms may be important sources of epithelium-derived NO throughout lung development.

Animals↗

Kinetics of 5-aminolevulinic acid-induced fluorescence in organ cultures of bronchial epithelium and tumor.

BACKGROUND: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. OBJECTIVE: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. METHODS: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. RESULTS: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. CONCLUSION: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma.

Aminolevulinic Acid↗

Structure and postnatal transformation of the intermediate epithelium lining the mouse nasopalatine duct.

In the epithelium lining the nasopalatine duct of the infant mouse, a transitional zone between the stratified squamous epithelium and the ciliated columnar one can be observed. The epithelium lining the transitional zone shows gradations ranging from the stratified squamous through the stratified cuboidal to the ciliated stratified low-columnar type, and gradually transforms into the stratified squamous epithelium with advancing ages. In the adult mouse, the nasopalatine duct is lined with the stratified squamous epithelium throughout up to the vicinity of the nasal cavity, and changes abruptly into the ciliated columnar epithelium lining the nasal cavity. It is suggested that the epithelium lining the transitional zone is identical with the 'intermediate epithelium' in the mouse nasopharynx and epiglottis.

Animals↗

A new concept regarding the origin of the junctional and crevicular epithelium in rat molars.

The substitution of the internal enamel epithelium by a squamous epithelium during tooth eruption has been studied histologically in rat molars. Just prior to eruption, cytolysis of the connective tissue covering the cusp tip determines hyperplasia in the oral epithelium. A conspicuous infiltration results. Infiltrated undifferentiated cells form distinct cords which seem to be attracted by the internal enamel epithelium. They reaggregate when they come into its contact and form an underlying epithelium. The process starts in the superficial part and progressively extends towards the cervix. Finally, the internal enamel epithelium is expelled when desquamation begins. The lack of mitoses in both stratum intermedium and internal enamel epithelium and the pyknosis observed in the former, clearly show that the cells of the embryonic dental bell do not take part in the formation of the squamous epithelium as some authors still suppose.

Ameloblasts↗