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Disappearance of desmosomal components in rat corneal epithelium during wound healing.

PURPOSE: Epithelial migration is essential for healing of the ablated corneal epithelium. To reveal the mechanism which enables the corneal epithelial cells to dissociate during migration, we investigated the immunolocalization of the components of the desmosome, which is the main constituent of the intercellular junction attaching the intermediate filaments to the cell surface, desmoplakin 1, desmoglein and plakoglobin, in the corneal epithelium during wound healing in rats. METHODS: Under general anesthesia with ether inhalation, Wistar rats (n = 48) underwent removal of the central corneal epithelium of one eye with a small trephine and a scalpel. After various intervals of healing (5 min; 1, 3, 6, 9, 12, 24, 48 h; 1 and 2 weeks), the animals were killed and the affected eye was excised. Cryosections of each anterior segment of the eye were fixed with cold acetone and treated with primary antibodies against desmoplakin 1, desmoglein and plakoglobin. Immunolocalization of these substances was visualized by the peroxidase-diaminobenzidine reaction. RESULTS: A marked immunoreactivity for these desmosome components was detected at the intercellular junction in the normal corneal and conjunctival epithelium. At 6-24 h after epithelial ablation, a weak immunoreactivity for desmoplakin 1 and plakoglobin was observed in the migrating epithelium. At 48 h after epithelial ablation, a marked immunoreactivity for these desmosome components was seen again. At 6-48 h after epithelial ablation, a weak immunoreactivity for desmoglein was observed in the migrating epithelium. At 1 week after epithelial ablation, a marked immunoreactivity for this desmosome component reappeared. The regenerated epithelium gradually exhibited normal immunolocalization of the proteins. CONCLUSIONS: The desmosome components were considered to be degraded or destroyed prior to epithelial migration and reconstructed during healing of the squamous epithelium.

Animals↗

Influence of epithelium and isoprenaline incubation on responsiveness of guinea-pig trachea to methacholine.

There are reports regarding harmful effect of long-term use of beta2-agonist drugs on asthma severity and airway responsiveness. In the present study, the responses of guinea pig trachea with intact and denuded epithelium (groups 1 and 2, n = 10) to methacholine as EC50 were measured in tissues nonincubated or incubated with 10 mumol/l isoprenaline during the resting period. The same protocol was performed in groups 3 and 4 (n = 5 for each group) with an additional 30 min rest time after isoprenaline incubation. The response of trachea with denuded epithelium (groups 2 and 4) to methacholine was significantly higher than that with intact epithelium both in incubated and nonincubated conditions (groups 1 and 3, p < 0.05 to p < 0.001). Incubation with isoprenaline caused a significant reduction in the tracheal response to methacholine in both the denuded groups (p < 0.005 and p < 0.001) and intact epithelium groups (p < 0.005 for both cases). The reduction in tracheal responsiveness to methacholine due to incubation in epithelium denuded trachea (groups 2 and 4) was nonsignificantly greater than that of intact epithelium tissues. There was no difference between groups 3 and 4 with those of groups 1 and 2 in both incubated and non incubated conditions. The maximum contractility response to methacholine was not different between tracheal chains with denuded and intact epithelium and did not change due to incubation with isoprenaline. The results of this study indicate reduction of tracheal response to methacholine due to incubation of tissues with isoprenaline, which was relatively more pronounced in epithelium denuded trachea.

Adrenergic beta-Agonists↗

Intermediate epithelium lining the mouse auditory tube.

In the newborn mouse, the auditory tube is lined throughout the pharyngeal orifice to the tympanic orifice with ciliated columnar epithelium. In the adult mouse, the tube is divided into membranous and cartilaginous parts. The membranous part is covered by the ciliated columnar epithelium, while the cartilaginous part by varying types of epithelium ranging from ciliated columnar to stratified squamous type. It is suggested that the varying types of epithelium correspond to the 'intermediate epithelium', and that ciliated columnar epithelium transforms in part to stratified squamous epithelium by passing through the intermediate epithelium.

Age Factors↗

Histamine tachyphylaxis in human airway smooth muscle. The role of H2-receptors and the bronchial epithelium.

The role of airway epithelium and H2-receptors in the development of histamine tachyphylaxis was studied using human isolated bronchial smooth muscle strips obtained from 18 patients undergoing thoracotomy. In epithelium-intact strips, a 38% reduction in the maximal contractile response (Emax) (p less than 0.002) and a 2.14-fold increase in the EC50 (p less than 0.02; n = 18) was observed after three separate histamine cumulative concentration effect curves (CCEC). In contrast, significant differences were not seen for either Emax (p greater than 0.4; n = 10) or EC50 (p greater than 0.26; n = 10) in epithelium-denuded strips. In separate experiments, both intact and denuded muscle strips were treated with the H2-receptor antagonist ranitidine (60 microM), either 30 min prior to the first or 30 min prior to the second histamine CCEC. In epithelium-intact strips, pretreatment with ranitidine caused a 1.8-fold increase in Emax in the initial CCEC (p less than 0.02), and both ranitidine schedules prevented tachyphylaxis (n = 8). In epithelium-denuded preparations, ranitidine did not enhance the responsiveness to histamine beyond that seen in untreated epithelium-denuded strips (n = 6). These data suggest that histamine-induced tachyphylaxis occurs in human airway smooth muscle and is mediated, at least in part, via H2-receptors resident on airway epithelium. In vivo, this may function as a protective mechanism, but damage to the epithelium and loss of H2-receptors may be significant in the development of histamine bronchial hyperreactivity as seen in asthma.

Bronchi↗

Regional distribution of Na,K-ATPase activity in porcine lens epithelium.

PURPOSE: It has been established that Na,K-ATPase activity is higher in lens epithelium than fibers. However, others have suggested the Na,K-ATPase enzyme may be inactive or absent in the central 10% of the epithelium. Studies were conducted to measure and compare Na,K-ATPase specific activity and to examine Na,K-ATPase protein expression in the anterior and equatorial regions of porcine lens epithelium. METHODS: Na,K-ATPase activity was determined by measuring the ouabain-sensitive rate of adenosine triphosphate (ATP) hydrolysis. Western blot analysis was used to detect Na,K-ATPase catalytic subunit (alpha) and glycoprotein subunit (beta) protein as well as beta-actin which was used as a loading control. RESULTS: Na,K-ATPase specific activity was more than two times higher in the equatorial epithelium than the anterior 50% of the epithelium. However, the abundance of Na,K-ATPase alpha1 isoform protein was similar in the two regions. Neither the alpha2 nor alpha3 Na,K-ATPase isoform could be detected in the anterior or equatorial epithelium, but Na,K-ATPase beta1 protein was detected in both regions. In contrast to the observed regional difference in Na,K-ATPase activity, the activity of a different P-type ATPase, plasma membrane Ca-ATPase (PMCA), was not significantly different in the anterior and central epithelium. Western blot analysis indicated the presence of two PMCA isoforms, PMCA2, and PMCA4. CONCLUSIONS: Na,K-ATPase activity is significantly higher at the equatorial region of the epithelium compared with the anterior, even though the level of Na,K-ATPase protein is similar in the two regions. It is possible that nonuniform distribution of functional Na,K-ATPase activity contributes to the driving force for circulating solute movement through the lens fiber mass.

Adenosine Triphosphate↗

Distinct populations of dendritic cells in the normal human donor corneal epithelium.

PURPOSE: To characterize dendritic cells (DC) in normal human corneal epithelium. METHODS: Normal human donor corneal epithelium was examined by fluorescence microscopy with single and double staining for multiple markers. Morphologic studies were also performed by confocal microscopy. HLA-DRa, CD1c, and CD16 mRNA expression in the corneal epithelium was examined by RT-PCR. CD45+ cells were separated from the corneal epithelium with magnetic beads and then were stimulated with TNF-alpha and lipopolysaccharide in vitro. RESULTS: CD45+ cells were mainly located in the basal-cell layer of the corneal epithelium and partly in the wing/surface layers. CD45-positive cell numbers were significantly higher in the peripheral cornea (3-6 mm from the center) than in the central cornea (0-3 mm from the center). All these cells expressed HLA-DR and CD11c but not CD3, CD11b, CD14, CD19, CD56, or CD66, suggesting that these were bone marrow-derived myeloid DC. Some DR+CD11c+ DCs from the periphery expressed CD1c and CD16. HLA-DRa, CD1c, and CD16 mRNAs were detected in normal corneal epithelium. These CD11c+ DCs did not express CD123, CD1a, DC marker (CMRF56), CD40, CD80, or CD86. When CD45+ cells were isolated from the corneal epithelium by magnetic cell sorting, CD40 and CD86 expression were detected after in vitro stimulation with TNF-alpha and lipopolysaccharide. CONCLUSIONS: These findings demonstrate that normal human corneal epithelium contains at least three DC phenotypes, with HLA-DR+ myeloid lineage CD11c+CD16- DCs as the main population plus a small number of CD11c+CD16+ DCs and CD11c+CD1c+ DCs. These cells can be discriminated from bone marrow-derived cells in the human corneal stroma.

Aged↗

Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ.

Teeth develop from composite organ rudiments that are formed through the interaction of oral epithelium and mesenchyme of the first branchial arch; cells of the former differentiate into enamel-secreting ameloblasts whereas those of the latter differentiate into dentine-secreting odontoblasts. Experimental analysis of odontogenic tissue interactions in mammalian embryos has focused on the late developmental stages of morphogenesis and cytodifferentiation; little is known about initial pattern-forming events, during which presumptive tooth-forming cells are specified and the sites of tooth initiation become established. It requires to be shown, for example, whether the mesenchymal cells of mammalian teeth are derived, like those of amphibians, from the cranial neural crest, and if so, whether these form a specified subpopulation in the neural folds. Alternatively, are they specified after migration into the mandibular arch, possibly by interaction with the oral epithelium? The developmental potentials of mouse embryo premigratory cranial neural crest cells (CNC - explanted from the caudal mesencephalic and rostral metencephalic neural folds) have been studied in intraocular homograft recombinations with various regions of embryonic surface ectoderm. Cartilage, bone and neural tissue developed in all combinations of CNC and epithelium. Teeth formed in combinations of CNC with mandibular arch epithelium but not in combinations of CNC with limb bud epithelium. Teeth also formed in combinations of mandibular arch epithelium with neural crest explanted from the trunk level. These results indicate that mammalian neural crest has an odontogenic potential but that this is not restricted to the crest of presumptive tooth-forming levels. Normal migration appears not to be a prerequisite for expression of odontogenic potential but this does require an interaction with region-specific epithelium. It is reasonable to infer that during normal development the neural crest that enters the mandibular arch is odontogenically unspecified before or during migration and that the oral epithelium is the earliest known site of tooth pattern.

Amelogenesis↗

Interaction of asbestos with metaplastic squamous epithelium developing in organ cultures of hamster trachea.

The normal mucociliary epithelium of the respiratory tract in chronic cigarette smokers often is replaced focally by a metaplastic squamous epithelium. Because asbestos workers who smoke have a substantially greater risk of bronchogenic carcinoma than nonsmokers, we hypothesized that interaction of asbestos with squamous epithelium might be a contributing factor. To address this question, an in vitro model was developed to study the interaction of asbestos with both mucociliary and squamous epithelium. Explants of tracheas from hamsters were cultured in either a chemically defined minimal essential medium, which maintains a differentiated epithelium, or a nutritionally complex medium, which encourages the development of squamous metaplasia. Scanning electron microscopy (SEM) was used to measure quantitatively the development of a squamous epithelial surface on the explants. The interaction of chrysotile and crocidolite asbestos with cells of the mucociliary and squamous epithelium was studied using both SEM and transmission electron microscopy (TEM). Long fibers of asbestos were cleared, whereas shorter fibers were phagocytized by cells of the mucociliary epithelium. In contrast, asbestos was phagocytized by superficial squamous cells regardless of fiber length, and fibers penetrated between intercellular junctions in the metaplastic epithelium. The relevance of these interactions to the induction of bronchogenic carcinoma is discussed.

Animals↗

Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

Animals↗

Ultrastructure and chloride cytochemistry of the hindgut epithelium in the larvae of the seawater mosquito, Aëdes togoi Theobald.

The hindgut of Aëdes togoi larvae adapted to various external salinities was studied by light and electron microscopy. The larvae's pyloric chamber and the ileum of the hindgut are surrounded by a thick muscular layer and lined with a very thin unspecialized epithelium. There is no detectable difference in the ultrastructural organization of the epithelium between seawater-adapted and freshwater-adapted larvae. The rectum and the anal canal are greatly dilated and densely tracheated and have a very thick, highly specialized epithelium. The rectal epithelium is characterized by shorter apical and longer basal infoldings closely associated with mitochondria, and a particulate coating on the apical infoldings. The intercellular spaces and the basal channels are tightly closed in the rectal epithelium of freshwater-adapted larvae, whereas widely dilated in that of 100 to 200% seawater-adapted larvae. The rectum seems to reabsorb water from excretory fluid when larvae are in hyperosmotic media. The anal canal epithelium possesses well-developed apical infoldings, which are coated with small particles an intimately associated with mitochondria. The basal infoldings are short. No perceptible difference in the ultrastructural organization of the epithelium was observed between seawater-adapted and freshwater-adapted larvae. The lumina of the apical infoldings of the anal canal epithelium in seawater-adapted larvae, however, demonstrated a strongly positive reaction to the cytochemical assay for chloride ions, whereas the reaction was very weak in freshwater-adapted larvae. Unlike salt-water-mosquito larvae of the other species, in which the rectum is considered to be concerned with the formation of hyperosmotic urine, the anal canal in A. togoi larvae seems to play an important role in excretion of excess ions in the haemolymph when adapted to hyperosmotic media.

Aedes↗

Ultrastructure of regenerating junctional epithelium in the monkey.

It has been established that after gingivectomy the junctional epithelium is reformed from the oral epithelium but there is little information on the regenerative potential of residual junctional epithelium. In this study reformation of the epithelial attachment in the monkey was followed ultrastructurally after surgical removal of all of, or of part of, the original junctional epithelium by internal or external bevel techniques respectively. In both circumstances a new epithelial attachment developed from the adjacent gingival oral epithelium and residual junctional epithelium appeared to persist as small nests of cells adjacent to the cemento-enamel junction. Epithelialization of the gingival wound was rapid, taking place in as little as 5 days after the partial removal of the junctional epithelium by the external bevel technique and by 10 days in wounds in which the junctional epithelium had been completely excised. This difference in the rate of epithelialization seemed to be primarily related to the quantity of coagulum and cell debris present, the greater amount remaining after the internal bevel technique tending to retard epithelial migration and reattachment.

Animals↗

Morphologic evidence of interactions between adult ductal epithelium of pancreas and fetal foregut mesenchyme.

First, tissue recombinants were used to determine the residual capability of adult endodermal pancreatic ductal epithelium to form islets. Second, adult epithelium was challenged by placing it between adult stroma and fetal mesenchyme to investigate the epithelial response (subsequently called challenge grafts). Trypsin was used to isolate adult mouse (heteroplastic) or rat (homoplastic) pancreatic ductal epithelium and fetal rat mesenchyme. All the adult epithelium was maximally stressed with alloxan to control for beta-cell contamination. Fetal mesenchyme was layered with epithelium in vitro for at least 48 h. Subsequently, the recombinants were grafted into nude mice and allowed to develop for 4-6 wk. To assess development, grafts were removed and fixed for both light and electron microscopy. In general, the grafts became organized into vesicles, tubules, and buds, many of which were in the form of vascularized isletlike structures. Epithelium responded with mitosis and intercellular adhesion. the range of cytodifferentiation varied. Culture time, age, and adhesiveness of the fetal mesenchyme and the amount of adult epithelium used in making the recombinants influenced the degree of differentiation. Analysis of fine structure of isletlike structures revealed cells with small electron-dense granules. These observations provide evidence for activation of endodermal epithelium taken from an adult mammal.

Animals↗

Autoimmunity against corneal antigens. I. Isolation of a soluble 54 Kd corneal epithelium antigen.

Corneal epithelium antibodies were detected in patients with corneal melting disease and uveitis using an immunofluorescence technique with cryostat sections of corneas obtained from various species (man, guinea pig, rabbit, mouse, rat, cow, pig). No differences in results were found using these various substrates, indicating that the autoimmune response is directed against common non-species specific corneal epithelium antigens. The serum of a patient with corneal melting disease, containing a high antibody titer against corneal epithelium was used to identify and isolate one of the bovine corneal antigens. A 54,000 dalton protein was isolated, which was shown to be the major protein present in the corneal epithelium. Absorption studies with other tissues taken from human eyes showed that cornea epithelium, cornea devoid of epithelium, ciliary body and retina contained material which cross-reacted with the isolated bovine corneal epithelium antigen, whereas iris and sclera showed no detectable cross-reaction. The incidence of autoantibodies directed against this antigen was investigated in patients with corneal melting disease, corneal transplantion and in uveitis patients using an ELISA and comparing the results with those obtained with the immunofluorescence assay on rabbit cornea sections. A positive ELISA was always associated with a positive immunofluorescence test. The presence of antibodies against the 54 Kd antigen as detected by the ELISA could be confirmed by immunoblotting in 7 out of 9 positive sera tested. A large number of sera showed a positive immunofluorescence test but a negative ELISA against the 54 Kd corneal epithelium antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Differential sensitivity of rat uterine growth and epithelium hypertrophy to estrogens and antiestrogens.

Triphenylethylene antiestrogens are considered weak estrogen agonists based on their limited ability to induce estrogen responses, in particular uterine growth. We compared the uterotrophic activity of naturally occurring and synthetic estrogens with that of antiestrogens by quantitating uterine wet weight and hypertrophy in the uterine luminal and glandular epithelium. Immature rats received five daily injections of either an estrogen (17 beta-estradiol [E2], diethylstilbestrol [DES], or ethynyl estradiol [EE]) or an antiestrogen (tamoxifen [TAM], monohydroxytamoxifen [OH-TAM], or clomiphene citrate [CC]) (0.001-100 micrograms/rat/day) subcutaneously in sesame oil and were sacrificed approximately 2 hr after the last injection. Both DES and EE increased uterine weight at doses between 0.01-100 micrograms/rat/day; E2 was about 10-fold less potent. The antiestrogens increased uterine weight only slightly. DES, EE, and the three antiestrogens each increased luminal epithelium hypertrophy to over 3-fold above that in controls. While the potencies of these synthetic compounds differed (DES = EE > OH-TAM > TAM = CC), each hypertrophic response occurred over two log doses, and the response curves displayed identical slopes. E2, however, required a range of four log doses to achieve the same degree of luminal epithelium hypertrophy. The three antiestrogens elicited glandular epithelium hypertrophy up to 2-fold above controls at the same doses that induced luminal epithelium hypertrophy; the order of potency was OH-TAM > TAM = CC. However, the three estrogens increased glandular epithelium hypertrophy only marginally. Thus, under dosing conditions commonly used to assess uterotrophic activity, these "antiestrogens" are complete, albeit less potent, estrogen agonists in the luminal epithelium and, unlike estrogens, induce hypertrophy in the glandular epithelium.

Animals↗

Difference of gene expression profiles between esophageal carcinoma and its pericancerous epithelium by gene chip.

AIM: To study the difference of gene expression between esophageal carcinoma and its pericancerous epithelium and to screen novel associated genes in the early stage of esophageal carcinogenesis by cDNA microarray. METHODS: Total RNA was extracted with the original single step way from esophageal carcinoma, its pericancerous epithelial tissue and normal esophageal epithelium far from the tumor. The cDNA retro-transcribed from equal quantity of mRNA was labeled with Cy5 and Cy3 fluorescence functioning as probes. The mixed probes were hybridized with two pieces of BioDoor 4 096 double dot human whole gene chip. Fluorescence signals were scanned by ScanArray 3 000 laser scanner and farther analyzed by ImaGene 3.0 software with the digital computer. RESULTS: (1) A total of 135 genes were screened out, in which 85 and 50 genes whose the gene expression levels (fluorescence intensity) in esophageal carcinoma were more than 2 times and less than 0.5 times respectively compared with the normal esophageal epithelium. (2) There were also total 31 genes, among then 27 and 4 whose expressions in pericancerous tissue were 2-fold up-regulated and 0.5-fold down-regulated respectively compared with normal esophageal epithelium. (3) There were 13 genes appeared simultaneously in both pericancerous epithelium and esophageal carcinoma, while another 18 genes existed in pericancerous epithelium only. CONCLUSION: With the parallel comparison among these three gene profiles, it was shown that (1). A total of 135 genes, Whose expression difference manifested as fluorescence intensity were more than 2 times between esophageal carcinoma and normal esophageal epithelium, were probably related to the occurrence and development of the esophageal carcinoma. (2). The 31 genes showing expression difference more than 2 times between pericancerous and normal esophageal epithelium might be relate to the promotion of esophageal pericancerosis and its progress. The present study illustrated that by using the gene chip to detect the difference of gene expression profiles might be of benefit to the gene diagnosis, treatment and prevention of esophageal carcinoma.

Carcinoma↗

Development of the vaginal epithelium showing estrogen-independent proliferation and cornification in neonatally androgenized mice.

Female mice of the C57 Black/Tw strain given 5 daily injections with 100 microng testosterone (T) or 5 alpha-dihydrotestosterone (DHT) from the day of birth showed estrogen-independent persistent proliferation and cornification of the vaginal epithelium in adulthood. The vaginal epithelium of the mice was essentially similar to that of the controls in histological structure during or shortly after neonatal injections of the androgens. In T- and DHT-mice aged over 20 days, however, a marked proliferation with or without superficial cornification took place in the epithelium lining the proximal and middle parts of the vagina (Müllerian vagina), while neither proliferation nor cornification occurred in the epithelium of the distal vagina (urogenital sinus vagina). On the second day of postnatal life in mice given a single injection with T on the day of birth, the mitotic activity in the epithelium of the middle vagina was heightened, but it dropped to the control level on the third day and remained low until 20 days. By contrast, the mitotic rates in the epithelium of the rest of the vagina in T-mice and of all parts of the vagina in DHT-mice were approximately the same as in the controls until 20 or 30 days. The mitotic rates in the epithelium of the Müllerian vagina were markedly elevated in T-mice at 20 days of age and DHT-mice at 30 days, and thereafter remained almost unchanged until 60 days of age. These results were different from the findings in mice given neonatal injections with the dose of estradiol-17 beta (E) capable of estrogen-independent vaginal cornification (Iguchi et al., 1976). The present finding seem to indicate that the mechanism involved in the induction of estrogen-independent vaginal changes by neonatal administration of androgen (T, DHT) is different from that following neonatal treatment with estrogen (E), although androgen and estrogen act directly on the vaginal epithelium of neonates.

Animals↗

Histological studies on early changes of the hamster gingival epithelium by N-nitrosomethylurea.

The effect of repeated intragastric administration of N-nitrosomethylurea on the molar gingival epithelium of the hamster was investigated both higtologically and histoautoradiographically. Thickening and downward proliferation of the gingival epithelium were evident from the second month of the treatment, in the attachment epithelium and interdental epithelium. Subsequently, the apical part of the crevicular epithelium, epithelium of the oral aspect of the gingiva, and the marginal crevicular epithelium thickened. About three months after the beginning of the administration, thickening, hyperkeratosis, and downward proliferation of the gingival epithelium were widespreas and proliferated epithelial cell nests were parakeratotic, often assuming a structure of keratotic cyst, which invaded the periodontium, accompanied with compressive resorption of the alveolar bone and involvement of bone marrows. Cellular atypia appeared three months after the first treatment, occasionally suggesting early malignancy. Epithelial proliferation was generally not accompanied with any distinct inflammatory change. In the autoradiographic analysis, it was clearly noticed that labeled cells had increased in each epithelial zone before the histological changes became evident- The results of the present experiment were discussed in reference to the pathogenesis of gingival carcinoma.

Animals↗

Transport of oxalate across the rabbit papillary surface epithelium.

PURPOSE: The renal papilla and pelvic recesses of the mammalian kidney are thought to be the anatomical sites of initial kidney stone formation. We studied oxalate transport across the renal papillary surface epithelium. MATERIALS AND METHODS: In vitro oxalate transport across the papillary surface epithelium was studied by dissecting it off of the papilla and mounting it in a modified Ussing chamber. Experiments were conducted using physiological Ringer's solution at 37C. Removal or appearance of radioactive oxalate from the solution bathing the apical papillary surface epithelium surface was used as a measure of transepithelial transport. RESULTS: When only the papillary surface epithelium apical surface was exposed to oxalate (17 micromol./l.), the apical to basolateral flux of oxalate was 7.1 +/- 1.5 nmol./cm.2 per hour. When only the basolateral side was perfused with oxalate, the basolateral to apical oxalate flux was 1.6 +/- 0.7 nmol./cm.2 per hour. When the apical and basolateral surfaces were exposed to oxalate, a net apical to basolateral flux of oxalate was 3.0 +/- 0.7 nmol./cm.2 per hour. There was almost complete inhibition of apical to basolateral oxalate transport when the experiments were conducted at 20C. Absorption of oxalate across the papillary surface epithelium was decreased by the addition of 1 mM. 4, 4'-diisothiocyanatsostilbene-2,2'-disulphonic acid (DIDS), independent of sodium, but reduced by the presence of chloride in the apical solution. Increasing the pH of the apical solution from 7. 4 to 7.8 also resulted in a significant decrease in papillary surface epithelium oxalate uptake. CONCLUSIONS: Rabbit papillary surface epithelium demonstrates oxalate absorption by mechanisms that may be similar to those described previously for renal and colonic epithelia. Absorption of oxalate across the papillary surface epithelium may have a role in the prevention of initial calcium oxalate stone formation within the pelvic recesses.

Animals↗