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Adenovirus-mediated gene transfer to the ocular surface epithelium.

Gene transfer to the ocular surface epithelium is of potential therapeutic value. It was determined whether a reporter gene can be introduced into the ocular surface epithelium in vitro (human cell lines), ex vivo (human tissues), and in vivo (rats) by treating with a recombinant, replication-deficient, adenovirus type 5. Human and conjunctival cell lines were cultured with various multiplicities of infection (MOI; 3.2x10(-5)-5x10(-1)) of adenovirus vector (Ad5:Adex1CAlacZ) containing the reporter gene lacZ (1.3-2.0x10(4) PFU ml-1). The ex vivo study used human corneal and conjunctival tissues obtained from an eye bank and during surgery. Non-specific upregulation of inflammatory cytokines of conjunctival epithelium infected by Ad5 was assayed and its suppression by steroids. For the in vivo study, Ad5 (5x10(5) PFU, 5-10 microliter) was applied to the eyes of 8-12-week-old cotton rats, which were enucleated 24 and 48 hr later. The maximum lacZ expression in vitro was demonstrated in the corneal epithelial cell line at 7 days (1x10(-1) MOI) and conjunctival epithelial cell line at 2 days (4x10(-4) MOI). Furthermore, lacZ was also expressed in the superficial corneal and conjunctival epithelium in the ex vivo study. IL-6, IL-8, and ICAM-1 expression from conjunctival epithelium by Ad5 was significantly inhibited by treatment with betamethasone (BM). For the in vivo study, only the conjunctival epithelium demonstrated beta-Gal activity at 24 and 48 hr after application. These data indicate that adenovirus vector is capable of directly delivering gene to the corneal and conjunctival epithelium, suggesting a variety of possible gene therapy uses. The concomitant application of steroid eye drops may avoid inflammation.

Adenoviridae↗

Spatiotemporal distribution of zonulae adherens and associated actin bundles in both epithelium and fiber cells during chicken lens development.

Zonulae adherens and associated actin bundles (ZA/AB) are believed to play a major role in epithelial folding and invagination during morphogenesis of neural tube and other vesicular structures. The lens morphogenesis is associated with the formation of the lens vesicle in which ZA/AB would be needed during the formation process. However, the existence of ZA/AB in the lens has never been established. In this study we report for the first time the existence of ZA/AB in both lens epithelium and fiber cells during embryonic development of chicken lens from E4 to E20. Light microscopy revealed contacts between the lens epithelium and primary fiber cells, and between the lens epithelium and secondary fiber cells at E4 and E11, respectively. Thin-section electron microscopy consistently revealed ZA/AB near both the apical ends of lens epithelial cells and primary fiber cells at E4. This arrangement manifests as a parallel pair of belt-like ZA/AB along the epithelium-fiber interface. In semi-tangential sections, a continuous belt-like ZA/AB was also evidenced in individual epithelial cells and fiber cells. Furthermore, the same ZA/AB arrangement was observed near both the apical ends of epithelial cells and secondary fiber cells at E11. Besides ZA/AB, macular-type fasciae adherens were distributed regularly between epithelial cells, between primary fibers, between secondary fibers, and between epithelium and both primary and secondary fibers. Immunofluorescence strongly and preferentially labeled N-cadherin at both the apical ends of lens epithelium and primary or secondary fibers at the corresponding ages, suggesting a direct association with the zonulae adherens. Also punctate N-cadherin labeling was commonly seen along various regions of primary and secondary fiber cells at different ages, and to a larger extent in the mature fibers of older lenses. This study suggests that: (1) ZA/AB located at the apices of lens epithelial cells may play a crucial role in the early stages of lens morphogenesis (e.g. lens vesicle formation); (2) ZA/AB of primary and secondary fiber cells originate from the epithelial cells during their elongation and differentiation; (3) owing to the restricted distribution of ZA/AB, abundant fasciae adherens are needed to maintain the structural stability of the epithelium and fiber cells during development and maturation; and (4) N-cadherin is the principle adhesion protein for both the zonulae adherens and fasciae adherens in the lens.

Actins↗

Phagocytic cells in the rat olfactory epithelium after bulbectomy.

The phagocytic cells in the rat olfactory epithelium were examined after unilateral bulbectomy. Immunohistochemistry using a monoclonal anti-macrophage antibody (OX42) and electron microscopy showed that macrophages were present in the olfactory epithelium of the operated side 1 day after bulbectomy. The average number was 5.9 OX42-positive cells/2 mm septal epithelium, compared with 2.9 in unoperated controls. At 3 days the number of macrophages/2 mm epithelium peaked at 16 and subsequently dropped to 2.1 at 7 days. The number of macrophages and the timing of their appearance in the olfactory epithelium during the 1st week after bulbectomy were related to the acute and massive death of olfactory cells. The number of macrophages returned to control levels at longer postoperative times (14, 30, 60, and 90 days). Most of the OX42-positive macrophages were the ED1-positive activated type. At 6 and 7 days after surgery large phagosomes containing cell debris were observed in the cytoplasm of supporting cells in the epithelium. The phagocytosis by supporting cells was more evident at 30, 60, and 90 days, in the chronic stages of cell death. The results indicate that macrophages are the major phagocyte in the olfactory epithelium during the 1st week after bulbectomy and that both supporting cells and macrophages participate in phagocytosis at longer survival times.

Animals↗

Immunohistochemical studies of sensory neurons in rat olfactory epithelium.

The olfactory sensory neurons undergo continuous turnover under normal physiological conditions. Injured olfactory sensory neurons are also replaceable. In this study, we investigated cellular differentiation and growth of sensory neurons in the rat's olfactory epithelium after nerve transection by using immunohistochemical staining with polyclonal or monoclonal anti-olfactory marker protein (OMP), anti-c-jun protein and anti-p53 protein antibodies. OMP is found exclusively in olfactory sensory neurons, while c-jun functions as a transcription factor. p53 protein functions as a negative regulator of cellular proliferation related to the apoptotic pathway induced by DNA damage. The olfactory epithelium sections incubated with anti-OMP antibody showed staining of mature neurons and axons in the epithelium. Nerve transection resulted in a significant reduction in neurons labelled with OMP. On the 9th day after operation, our study indicated some recovery with an increasing number of neurons expressing OMP. In control animals without nerve lesions, c-jun protein immunoreactive neurons were present in the olfactory epithelium adjacent to the basal region. Following days 1 and 3 after nerve transection, no expression of c-jun protein was seen in neurons of the epithelium. On day 9 after transection, neurons in some basal areas indicated expression of c-jun protein. The immunolocalization demonstrated that p53 protein was present in some neurons located on the upper part of the olfactory epithelium. In contrast, an abundance of neurons expressing p53 protein was evident in the olfactory epithelium 1 and 3 days after nerve transection, indicating more cell deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypotonic solutions induce epithelium-dependent relaxation of isolated canine bronchi.

The present study was designed to investigate the effect of changes in osmolarity on the modulatory role of the respiratory epithelium on the underlying smooth muscle. Canine bronchial segments with or without epithelium were perfused intraluminally with modified Krebs-Ringer bicarbonate solution. The transluminal isometric tension was recorded by means of stirrups passed through the bronchial wall. During contractions to extraluminal carbachol, the tissues with epithelium exhibited epithelium-dependent relaxations to hypotonic solution given intraluminally. The level of relaxation was dependent on the osmotic pressure. No significant difference was noted between relaxations due to hypotonic solution made by mixing the Krebs-Ringer solution with distilled water and those made by decreasing the concentration of sodium chloride. The epithelium-dependent relaxations could not be blocked by the antagonists or blockers of cyclo-oxygenase, endothelium-derived relaxing factor, alpha-adrenoceptors, beta-adrenoceptors, and sodium channels. No evidence for the release of a relaxing factor into the bronchial lumen was found in bioassay study. When the preparation was stimulated with hypertonic solutions prepared by adding mannitol or urea, similar relaxations were induced in tissues with and without epithelium. These observations suggest that changes in osmolarity affect the responses of canine bronchi to carbachol and that the epithelium modulates the responses of airway to hypotonic solutions.

Airway Resistance↗

Changes in cytokeratin expression accompany squamous metaplasia of the human respiratory epithelium.

To determine the characteristics of metaplastic changes of the nasal respiratory epithelium, the distribution of individual cytokeratins (CKs) was studied immunohistochemically and by two-dimensional gel electrophoresis. The authors define four types of changes of the normal pseudostratified columnar epithelium: (1) transitional pseudostratified epithelium (first unusual CK.: no. 13); (2) stratified columnar epithelium (increased expression of CKs 4 and 13; CKs 7, 8, 18 and 19 reduced); (3) stratified squamous epithelium, nonkeratinized (appearance of CK 16); and (4) stratified squamous epithelium, keratinized (expression of CKs 1 and 10, variable CK5 and 14 patterns in basal cells). These phenotypes were found simultaneously within single specimens, resulting in apparent overall variability in the immunohistochemical staining patterns. Spatially, changes in CK expression towards "normal" parts were not abrupt but rather gradual. Biochemical data confirmed the immunohistochemical findings and added CK 6 to the pattern of altered nasal mucosa. The findings of this study suggest a stem cell metaplasia in the nasal epithelium which is based on its inherent bimodal developmental programme. A gradual loss of normal respiratory epithelial differentiation, as seen by the loss of CKs 7, 8, and 18, was paralleled by the appearance of squamous epithelial type CKs, e.g. the expression of CKs 1, 10 and 13. Basal cell types CKs 5, 14, 17 and 19 were maintained during this process. Implications of these results for general concepts of CK expression in the metaplastic process are discussed.

Adolescent↗

Morphometric epididymal epithelium analysis in obstructive azoospermic men: predictive values in fertilization rates.

PURPOSE: Our purpose was to determine the obstructed epididymal epithelium morphometric state and to elucidate the influence of morphometric parameters on the fertilizing ability of aspirated spermatozoa. METHODS: During MESA with IVF, epididymal tissue samples were carefully dissected, fixed, and prepared for morphometric analysis. The epithelium of the three regions was studied: head, body, and tail (when present). The total area/luminal area ratio, epithelium thickness, and stereocilium length were measured. RESULTS: We have found significant differences in the total area/luminal area ratio, epithelium thickness, and stereocilium length in obstructed epithelium length > 4 versus 0.5-2 cm (P < or = 0.01). Epithelium thickness and stereocilium length were significantly lower when no fertilization was observed in IVF. CONCLUSIONS: These results suggest that morphometric data of obstructed epididymis epithelium can be used as a means of explaining the failure of IVF with epididymal spermatozoa.

Cell Separation↗

The fine structure of pigment epithelium of the iris in capsular glaucoma.

An electron microscopic study was performed on the pigment epithelium of the iris in 13 patients with capsular glaucoma. Pseudoexfoliative material (PE) was often observed in small depressions or indentations of the cell membrane of the posterior pigment epithelium. PE was also found in the region where the cell membrane was indistinct and took a course perpendicular to the surface of the cell membrane. Serial sections revealed no PE in the cytoplasm of the posterior pigment epithelium. Furthermore, the PE found extracellularly was continuous with the cell membrane. Three stages were distinguished in the pigment epithelium as capsular glaucoma progressed. At an early stage (stage 1), the number of infoldings in the posterior pigment epithelium increased, and PE was found at that site. In a more advanced stage (stage 2), the cytoplasmic processes increased in number and the basement membrane became discontinuous. In a further advanced stage (stage 3), a large amount of PE was found in the posterior chamber. The intercellular space between two adjacent pigment epithelial cells increased and the cytoplasmic processes gradually disintegrated. Only one significant correlation was found between the glaucoma stage and the stage of changes in the pigment epithelium. No associations were found between the stage of changes in the pigment epithelium and patient age or gonioscopic findings.

Aged↗

Heterogeneity in epithelium-dependent responses.

The airway epithelium exerts a profound influence on the responsiveness of bronchial smooth muscle to both contracting and relaxing agents. This may be due to the release of an epithelium-derived factor or factors. There is a considerable heterogeneity in the effects of the epithelium between orders of bronchi, between species, and between pharmacologic agents. Such heterogeneity may reflect variations in the release and/or effect of the epithelium-derived relaxing factor(s). This report demonstrates that: (1) there is a basal and a stimulated release of the factor, (2) the prominence of different types of release varies between species, (3) the effect of the epithelium on relaxation of bronchial smooth muscle is greatest in the presence of high degrees of cholinergic tone, (4) the effects of the epithelium are not mediated via cyclic GMP, and (5) the epithelium-derived relaxing factor is not nitric oxide.

Acetylcholine↗

DNA ploidy and proliferative activity of human pulmonary epithelium.

DNA ploidy and distribution has been determined in normal and abnormal bronchial, bronchiolar and alveolar epithelium from 22 patients, aged between 0 and 85 years, 9 of whom had received chemotherapy for malignant disease. The DNA ploidy was diploid in all the specimens examined. The S + G2/M fraction was significantly greater in diseased than normal bronchial trees. In the bronchial epithelium, mean values +/- the standard deviation (SD) were 5.5 +/- 2.2% vs 1.1 +/- 0.6%, in bronchiolar epithelium 4.6 +/- 1.6% vs 1.0 +/- 0.9% and in alveolar epithelium 4.6 +/- 1.6% vs 0.8 +/- 0.5%. The highest S + G2/M value of 8.9% was obtained from inflamed bronchial epithelium. Polyploid cells up to the octaploid range occurred infrequently but their incidence was slightly increased to between 0.16% and 0.9% in diseased lungs and in patients who had received chemotherapeutic drugs. It was concluded that (1) non-cancerous drugs. It was concluded that (1) non-cancerous pulmonary epithelium is diploid, that (2) pulmonary epithelium shows steady-state renewal at all ages and polyploid cells are rare under normal conditions and that (3) the S + G2/M fraction increases up to approximately 10% in reactive proliferative states.

Adolescent↗

Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation.

AIMS/HYPOTHESIS: Monocytes and macrophages accumulate in the lesion of the diabetic retina, which are most likely involved in the progression of diabetic retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous fluids were associated with the severity of proliferative diabetic retinopathy. Recently, pigment epithelium-derived factor has been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, a role of pigment epithelium-derived factor in monocyte recruitments in diabetic retinopathy remains to be elucidated. In this study, we investigated effects of purified pigment epithelium-derived factor on AGE-induced reactive oxygen species generation, MCP-1 mRNA up-regulation and protein production in human cultured microvascular endothelial cells. METHODS: The intracellular formation of reactive oxygen species was measured using the fluorescent probe CM-H(2)DCFDA. MCP-1 gene expression was analysed in quantitative reverse transcription-polymerase chain reaction. Monocyte chemoattractant protein-1 production by microvascular endothelial cells was measured with an ELISA system. RESULTS: AGE increased intracellular reactive oxygen species generation in microvascular endothelial cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive oxygen species generation in a dose-dependent manner. An anti-oxidant, N-acetylcysteine, or pigment epithelium-derived factor completely prevented the AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in microvascular endothelial cells. CONCLUSIONS/INTERPRETATIONS: Pigment epithelium-derived factor inhibits the AGE-induced reactive oxygen species generation and the subsequent increase in MCP-1 production in microvascular endothelial cells. Our study suggests that substitution of pigment epithelium-derived factor could prevent the progression of diabetic retinopathy by attenuating the deleterious effects of AGE.

Cells, Cultured↗

Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy.

AIMS/HYPOTHESIS: Retinopathy is the most common microvascular complication of diabetes. Our aim was to address the predictive value of pro-angiogenic and anti-angiogenic markers for progression of retinopathy. METHODS: Aqueous humor was collected at cataract surgery from 32 diabetic patients who had no or very mild retinopathy (ETDRS stage </=20) and 33 normoglycaemic control subjects. Content of pro-angiogenic vascular endothelial growth factor and angiogenic inhibitor pigment epithelium-derived factor were determined. ANGIOGENIC activity was quantified by measuring its effect on the migration of capillary endothelial cells. The predictive value of the initial level of these markers for progression of retinopathy was studied by following the probands for a maximum of 75 months. RESULTS: In the aqueous fluid content of vascular endothelial growth factor was increased in diabetic patients (mean values 492 versus 292 pg/ml; p=0.0052), and pigment epithelium-derived factor values were decreased (mean values 1740 versus 3680 ng/ml; p=0.0058) compared to control subjects. Of the diabetic patients ten progressed during follow-up (ETDRS stage >47B). This subgroup showed lower pigment epithelium-derived factor content when compared to non-progressors and control subjects. Migratory activity in samples of patients from the control group and in diabetic patients without progression was generally inhibitory due to pigment epithelium-derived factor. Inhibition was blocked by neutralizing antibodies to pigment epithelium-derived factor. In diabetic patients initial angiogenic activity was higher in those who later developed retinopathy (vs. controls p=0.00005; vs. no progressors p=0.0003). Both pigment epithelium-derived factor and migratory response predicted progression. CONCLUSION/INTERPRETATION: Pigment epithelium-derived factor is an important negative regulator of angiogenic activity of aqueous humor. Its content in the aqueous humor of diabetic patients strongly predicts who among them will develop progression of retinopathy.

Aged↗

[Biomorphometry of corneal epithelium with slit lamp-adapted optical coherence tomography].

INTRODUCTION: The purpose of this study was to evaluate the biomorphometry of the corneal epithelium with slitlamp-adapted optical coherence tomography (OCT). PATIENTS AND METHODS: In a clinical study, slitlamp-adapted OCT of the cornea was performed in 15 patients before and immediately after therapeutic corneal abrasion. Central corneal epithelium thickness measurements were compared to the pre- and postoperative central corneal thickness. RESULTS: Preoperatively, the corneal epithelium could be visualised from the highest OCT light reflections at the interfaces air-tear film and epithelium-Bowman's membrane. The preoperative mean geometrical central epithelial thickness determined with OCT ranged from 65 +/- 12 microns to 72 +/- 14 microns (45-92 microns). The mean difference of the pre- and postoperative central corneal thickness was 48 +/- 19 microns (9-79 microns). This resulted in a deviation from the direct epithelial thickness measurements of 26-33%. The reproducibility of the geometrical epithelial thickness was +/- 9 microns. CONCLUSIONS: Slitlamp-adapted OCT enabled a noncontact evaluation of the corneal epithelium. The difference between direct and indirect corneal epithelium thickness measurements could be related to the partial optical inclusion of the precorneal tear film and the Bowman's membrane. With some restrictions the biomorphometry of the corneal epithelium with slitlamp-adapted OCT seems to be a valuable technique to monitor therapeutical and refractive procedures of the cornea.

Adult↗

C-type natriuretic peptide and its receptor are downregulated in pulmonary epithelium following birth.

C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family and acts through the membrane bound guanylyl cyclase linked natriuretic peptide receptor B (NPR-B) to increase intracellular cGMP. Activation of the CNP/NPR-B pathway in pulmonary epithelium has been linked to the inhibition of amiloride-sensitive sodium absorption and to the stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR). Given the importance of ion movement across the pulmonary epithelium of the fetal and newborn lung, we sought to examine the expression of CNP and NPR-B in pulmonary epithelium of the developing fetal lamb and following the transition to air breathing. Lambs were sacrificed at 100 and 136 days of gestation and at 3 days, and 4 weeks after full term delivery. Lung sections were immunostained for CNP and NPR-B. At 100 days of gestation, staining for CNP and NPR-B was absent within all pulmonary epithelium. At 136 days of gestation, prominent staining for both CNP and NPR-B was seen within alveolar type II cells, non-ciliated cells of the distal airways (Clara cells), and ciliated epithelium of the upper airways. At both 3 days and 4 weeks following birth, staining for CNP and NPR-B was absent in alveolar type II cells, ciliated bronchial epithelium and was markedly reduced in Clara cells. The presence of CNP and NPR-B within the pulmonary epithelium in the nearterm fetal period and its rapid downregulation following birth suggests that CNP may contribute to the maintenance of the fluid-filled lung through the regulation of trans-epithelial ion flux.

Animals↗

Functional anatomy of human lacrimal duct epithelium.

Resorption of tear fluid in the lacrimal ducts has hitherto been controversial; one reason for this has been insufficient knowledge of the anatomical structure and function of the lacrimal duct epithelium. The present study analyzes the structure of lacrimal duct epithelium by means of histological, histochemical, immunohistochemical and electronmicroscopical methods and draws a conclusion about its physiological function regarding its role in immunodeficiency. Investigations were performed on 31 lacrimal systems of 17 male and 14 female individuals (aged 54-88 years). Lacrimal ducts are surrounded by a wide-ranging cavernous system, which is embedded in an osseous canal between the maxilla and the lacrimal bone. The internal wall of the lacrimal canaliculi is lined by a stratified epithelium. The lacrimal sac and nasolacrimal duct contain a double-layered epithelium, which rests on a broad basement membrane. In their apical part epithelial cells contain large lipid droplets and secretory vacuoles. Epithelial cells are faced by microvilli and some tufts of kinociliae are also visible. Goblet cells are integrated in the epithelium as solitary cells or in a characteristic arrangement of several cells. The secretory product of these cells contains carbohydrates including fucose and sialic acid. Inside the surrounding cavernous system serous glands are found that open their excretory ducts into the lacrimal sac and nasolacrimal duct. Some T- and B-lymphocytes and macrophages may be demonstrated immunohistochemically in the submucosa partly penetrating the epithelium. Synthesized mucins of goblet cells form a specialized protective layer on the epithelium of the lacrimal ducts, which functionally serves for a simplified drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells, the protective layer plays a role in antigen defense and prevents invasion of pathogenic agents. The facing of epithelial cells by microvilli gives hints of re-absorption of lacrimal fluid inside the lacrimal ducts.

Aged↗

Silica gel dessication of amniotic membrane with related epithelium cells for ocular surface reconstruction.

Cornea reparative regeneration when in various pathological states needs creating certain conditions to intensify the potential of regional stem cells mitotic activity. AIMS OF THE RESEARCH: To find out the degree of the epithelium AM preservation after preliminary processing and conservation by means of dehydration over silica gel with further sterilization; to study the effectiveness of clinical treatment of AM conserved in the surroundings with vital ability epithelium and AM dried over silica gel. MATERIALS AND METHODS: There was carried out an investigation of 18 samples of native amnion treated with antibiotics and 18 total surface amnion samples conserved by drying over silica gel and then sterilized by gamma rays. Clinical experiments were carried out on patients with severe chemical and thermal burns--18 people (21 eyes). After the burn trauma all the patients underwent the standard procedure of necrectomy, the covering of the eyeball with amniotic membrane dried over silica gel. CONCLUSION: The drying out of the amniotic membrane over silica gel on frames without being fixed on nitrocellulose paper makes the process of the amniotic membrane conservation simpler and makes it possible to preserve its unique biological qualities. The effectiveness of the regeneration of epithelium tissue of the eyeball surface with amniotic membrane dried over silica gel without the vital capacity cells of the epithelium layer is analogous to the regeneration of epithelium cells with amniotic membrane with vital capacity cells. With eye burns AM coverage hinders the formation of rough conjunctiva cicatrix, provides a favorable out-of-cell matrix substrate for epithelium migration and leads to quicker regeneration of one's own epithelium, makes further visual rehabilitation simpler.

Amnion↗

Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle.

The influence of the epithelium on the reactivity of guinea-pig tracheal smooth muscle in vitro was investigated. Mechanical removal of the epithelium produced contrasting effects on methacholine-, histamine- and K+-induced contractions of tracheal strips. Epithelium removal resulted in 2.1-fold shifts to the left of histamine and methacholine concentration-response curves, and an increase in the maximum response to histamine; the maximum response to methacholine was unaffected. Epithelium removal had little effect on the sensitivity, but decreased the maximum response to K+. The results suggest that inhibitory and excitatory factor(s) are released from epithelial cells, and that these factors modulate the reactivity of the smooth muscle. Indomethacin (1 microM) produced in epithelium-containing preparations qualitatively identical effects on the sensitivity to methacholine and on the maximum response to histamine as removal of the epithelium. However, indomethacin was without effect on the sensitivity to histamine in the presence or absence of the epithelium. Alterations in the production or release of epithelial cell-derived factors may contribute to the airway hyperreactivity observed in respiratory disorders.

Airway Resistance↗

Tissue-specific expression of keratin proteins in human esophageal and epidermal epithelium and their cultured keratinocytes.

In contrast to the simplified keratin content of bovine, rabbit, and rat esophageal epithelium (composed mainly of a 57 and 46 or 51 kD keratin, depending on the animal species), human esophageal epithelium contained a quantitatively different array of keratin proteins, ranging in molecular weight from 37 to 61 kD. The pattern of keratin proteins from human esophageal epithelium differed qualitatively and quantitatively from that of human epidermis. Human esophageal epithelium lacked the 63, 65, and 67 kD keratins characteristic of human epidermis, consistent with the absence of a granular layer and an anucleate stratum corneum. Moreover, human esophageal epithelium contained a distinctive 61 kD keratin protein which was either not present or present in only small amounts in human epidermis and variable amounts of a 37 kD keratin. Whereas the 56, 59, and 67 kD keratins were the most abundant keratins in human epidermis, the 52, 57, and 61 kD keratins predominated in human esophageal epithelium. During in vitro cultivation, both human epidermal and esophageal keratinocytes produce colonies which are stratified, but the morphologic appearance of these cultured epithelia differs. Only cultured human epidermal keratinocytes contain keratohyalin granules in the outermost layers and a prominent 67 kD keratin on immunoprecipitation. Otherwise the keratin contents appear similar. In conclusion, human esophageal epithelium exhibited intertissue and interspecies differences in the pattern of keratin proteins. During in vitro cultivation, human esophageal keratinocytes retained some aspects of their distinctive program of differentiation.

Animals↗