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[Structure of the epithelium of the parasitic turbellaria Notenera ivanovi (Turbellaria: Fecampiida)].

The ultrastructure of the epithelium in Notentera ivanovi (Turbellaria, Fecampiida) has been studied. Notentera ivanovi lacks the digestive system but has a pad of the epidermal cells on the dorsal side of the body, which seems to be similar to the digestive epidermis on LM. Both the ventral and dorsal epithelium are cellular, ciliated and not insunk (fig. 1, a). The ultrastructure of the ventral and dorsal epithelium is similar in essential features. The cells bear abundant microvilli, cilia and are very rich in mitochondria, but the cytoplasm does not contain lysosomes and shows no other indications of phago- or pinocytosis. The basal membrane of epithelial cells forms deep invaginations (fig. 1, [symbol: see text]), partly with dilations (fig. 1, a; 2, a) containing the lamellated material (3, [symbol: see text]). In the basal part of the cells the numerous Golgi apparatus and rare cysternae of the smooth endoplasmic reticulum were observed (fig. 2, a, [symbol: see text]). The epithelium consists of several types of cells, which differ in the structure of secretory granules. The most abundant type of cells contains the granules with the rough-fibrillated content (fig. 1, a; 2, [symbol: see text]; 3, a). The cells of this type cover most part of the body. In some cells the content of such granules becomes condensed and electron-dense granules appear (fig. 3, a, [symbol: see text]). Another type of cells contains the giant granules with the rough-fibrillated content (fig. 3, [symbol: see text]). Third type of the secret is the granules with the finely fibrillated content which is ejected by exocytosis. The cells of the second and third types form a separate areas of the epithelium of the dorsal side of the body but occasionally were observed in the ventral epithelium too. The epithelium of N. ivanovi differs from that in Kronborgia by the abundance and diversity of secretory contents. The role of the epithelium in the digestion remains conjectural. It seems to be mainly the suckering tissue transporting the low molecular nutrients.

Animals↗

Alterations of the glomerular epithelium in acute aminonucleoside nephrosis. Evidence for formation of occluding junctions and epithelial cell detachment.

The visceral glomerular epithelium of rats made nephrotic by daily injections of puromycin aminonucleoside was examined from the time of onset of proteinuria (day 6) to the time when many animals die (day 15) in order to establish the chronology of the pathologic alterations which occur during the course of the disease. In addition, the structure of the residual epithelial slits was examined using special fixatives and freeze-fracture. Changes seen early in the disease (7 to 9 days) are: (1) a reduction in the number of foot processes and filtration slits; (2) occurrence of occluding junctions in many of the residual slits coupled with displacement of the slit diaphragms; (3) thinning of the dense central portion of the basement membrane (lamina densa) with a corresponding widening of the space (lamina rara externa) between it and the epithelium; (4) heightened epithelial pinocytosis with increased numbers of protein absorption droplets or lysosomes. In freeze-fracture preparations the occluding junctions were seen to be limited in extent and made up of only a few strands, indicating they are incomplete and represent occluding maculae or fasciae rather than zonulae. Later on in the disease (10 to 15 days) no further changes in the number or arrangement of slits is evident, but other alterations occur: (1) denuded regions of basement membrane are seen where there is initially partial and eventually complete detachment of the epithelium from the basement membrane; (2) increasing numbers of large vacuoles or phagosomes and decreasing numbers of fully condensed lysosomes are present; and (3) basement membrane-like material is seen in the spaces between the partially detached epithelium and basement membrane. The new findings in this study are: (1) the clarification of early (reversible) versus late (probably irreversible) changes in the glomerular epithelium in a acute aminonucleoside nephrosis; (2) delineation of the structure of the residual epithelial slits; (3) the description of progressive loosening of the attachment between the epithelium and the basement membrane leading to focal or complete epithelial cell detachment; (4) the presentation of evidence indicating that exhaustion of the lysosomal system of the glomerular epithelium (in protein absorption and concentration) occurs late in the disease. The available evidence is summarized and indicates that the glomerular basement membrane, the main glomerular filter, is defective in aminonucleoside nephrosis and allows increased protein leakage. However, it seems likely that the main site of action of aminonucleoside is on the epithelium leading to the production of defective basement membrane.

Animals↗

Influence of epithelium on the reactivity of guinea pig isolated, perfused trachea to bronchoactive drugs.

The mechanisms by which the epithelium affects reactivity of guinea pig trachealis to agonists were examined using the isolated, perfused trachea preparation. Contractile agonists (acetylcholine, methacholine, carbachol or histamine) were more potent when applied to the serosal (extraluminal, EL) surface compared to the mucosal (intraluminal, IL) surface, and the IL maximum responses to these agents were smaller. In epithelium-denuded tracheae, IL reactivity to the agonists was increased to the EL level. Physostigmine (10(-7) M) increased the EL and IL potency of acetylcholine to that of carbachol (+/- epithelium), and elevated the IL acetylcholine maximum response (+ epithelium); the relative role of epithelial acetylcholinesterase could not be defined. Indomethacin (3 x 10(-6) M) increased, in an epithelium-dependent manner, the IL acetylcholine, carbachol and histamine maximum responses to the EL level. Phentolamine plus propranolol (both 10(-6) M) potentiated the IL maximum response to methacholine, Isoproterenol also was more potent extraluminally than intraluminally, and the EL and IL maximum responses were similar. IL isoproterenol reactivity was elevated to the EL level in rubbed tracheae. Corticosterone (5 x 10(-5) M) potentiated EL and IL responses to isoproterenol (+/- epithelium); the relative role of epithelial extraneuronal uptake could not be delineated. The epithelium reduces reactivity to mucosally applied drugs by acting as a diffusion barrier. In addition, responses to mucosally administered contractile agonists are inhibited by a physiological antagonism caused by modulatory prostanoids, catecholamines and, possibly, epithelium-derived relaxing factor.

Animals↗

Cytokeratin patterns in corneal, limbal, and conjunctival epithelium. An immunofluorescence study with PKK-1, 8.12, 8.60, and 4.62 anticytokeratin antibodies.

The authors examined immunofluorescently the specific cytokeratin staining patterns of corneal, limbal, and conjunctival epithelium with PKK-1, 8.12, 4.62, and 8.60 monoclonal anticytokeratin antibodies. Observations were made on unfixed frozen postmortem human tissue. The PKK-1 antibody stain was observed in all layers of corneal epithelium but only in suprabasal layers of limbal and conjunctival epithelium. By contrast, the 8.12 antibody stain was observed only in the superficial layer of corneal epithelium but through all layers of limbal and conjunctival epithelium. The 4.60 antibody stain was seen in focal areas of corneal and limbal epithelium and through all layers of conjunctival epithelium. The 8.60 antibody stain was not present in the three epithelia. These immunofluorescence studies showed unique cytokeratin patterns among layers in corneal, limbal, and conjunctival epithelium.

Adult↗

Postnatal transformation of the epithelium lining the nasolacrimal duct of the mouse.

The nasolacrimal duct of the newborn mouse was lined with the stratified cuboidal epithelium, while in the mouse after 15 days of age the epithelium was stratified squamous. Further, in the adult mouse the epithelium could not be classified definitely as typical stratified squamous epithelium, but was somewhat modified. It is suggested that the stratified cuboidal epithelium corresponds to the "intermediate epithelium (NAKANO 1986)", and transforms into the modified stratified squamous epithelium with passing through the typical stratified squamous epithelium.

Animals↗

Influence of epithelium on guinea pig airway responses to tachykinins: role of endopeptidase and cyclooxygenase.

We have studied the effect of epithelium removal on the contractile responses to exogenous tachykinins and to endogenous tachykinins released by capsaicin in guinea pig trachea. We also studied the effects of inhibition of endopeptidase (by phosphoramidon, 10 microM, and thiorphan, 100 microM), and of inhibition of cyclooxygenase (by indomethacin, 5 microM) on these responses. The order of potency of exogenous tachykinins was neurokinin A (NKA) greater than neurokinin B (NKB) greater than substance P (SP). Epithelium removal enhanced the sensitivity and magnitude of the contractile response to SP, and to a lesser extent NKA and NKB. Capsaicin induced only a weak contractile response in guinea pig trachea. Phosphoramidon and thiorphan increased the sensitivity to SP, but had no effect on acetylcholine responses. The leftwardshift due to epithelium removal was reduced, but not abolished, by phosphoramidon and thiorphan. NKA- and NKB-induced contractions were also enhanced significantly by phosphoramidon. The effect of epithelium removal was abolished for NKA, but not for NKB. Phosphoramidon also increased significantly the contraction to capsaicin in the presence of epithelium, without altering the response obtained in the absence of epithelium. Indomethacin potentiated the sensitivity and maximal contractile response to all the tachykinins with the greatest effect on SP responses, and to capsaicin. The combination of indomethacin with phosphoramidon or thiorphan abolished the effect of epithelium removal for all the tachykinins. We conclude that the effects of exogenous and endogenous tachykinins are enhanced by removal of epithelium and by inhibition of metalloendopeptidase and cyclooxygenase, suggesting that tachykinins may be degraded by epithelial enzymes, and may release relaxant prostanoids in airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chondrogenesis of mandibular mesenchyme from the embryonic chick is inhibited by mandibular epithelium and by epidermal growth factor.

This study documents the role of mandibular epithelium and epidermal growth factor (EGF) in the initiation, maturation and maintenance of Meckel's cartilage using percent 3H-thymidine-labelled cells as an index of proliferative activity and distribution of labelled cells, chondrocyte size and relative amount of extracellular matrix as indices of chondrogenesis. Mandibular mesenchyme from embryos of H.H. stages 18, 22, 25 was cultured for 2 to 10 days (a) unseparated from mandibular epithelium, (b) in isolation, or (c) after recombination with mandibular epithelium in the presence or absence of 5-40 ng/ml EGF. Epithelium delayed both initiation of chondrogenesis and maturation of already formed cartilage. The 3H-thymidine-labelling index was reduced in cartilage that differentiated in the presence of mandibular epithelium. Epithelium influenced the timing of mesenchymal differentiation (a) by delaying cytodifferentiation through prolonging high levels of proliferation, and (b) by directly affecting differentiation itself. EGF, especially at 10-20 ng/ml, affected both proliferation of mesenchyme and chondrogenesis in mesenchyme cultured with or without epithelium. All observed effects of epithelium on intact tissues could be duplicated by exposing isolated mesenchyme to EGF at 10 ng/ml, i.e. a role for EGF in chondrogenesis is suggested.

Animals↗

Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells.

A panel of monoclonal antibodies that phenotypically define stages of normal human thymic epithelial (TE) cell maturation was used to compare thymic epithelium of nine thymomas with hyperplastic thymic epithelium in myasthenia gravis (MG) and thymic epithelium of normal thymuses. It has been shown previously that normal thymic epithelial cells express antigens of early TE cell maturation (A2B5, TE-4) throughout thymic ontogeny and acquire antigens 12/1-2, TE8, and TE-15 at 14 to 16 weeks of fetal gestation. Hyperplastic MG thymic epithelial cells expressed TE antigens in phenotypic patterns similar to that seen in normal postnatal thymus, ie, TE in subcapsular cortex and medulla was TE4+, A2B5+, and 12/1 - 2+ and Hassall's bodies were reactive with antibodies TE8 and TE15. In contrast, thymic epithelium in primary mediastinal thymomas was TE4+, A2B5+, TE8-, and greater than 75% of thymoma epithelium was 12/1 - 2-, a thymic epithelial phenotype similar to that seen on normal fetal thymic epithelium at 14 to 16 weeks fetal gestation. In one subject with a mature epithelial histologic pattern, thymoma epithelium was found to be strongly TE8+, a phenotype suggestive of a later stage of TE maturation. Lymphocytes in five of seven thymomas with immature thymic epithelial cells predominantly expressed immature thymocyte phenotype while two thymomas with immature epithelial phenotype showed a predominance of Langerhans cells and surrounding lymphocytes expressing a mature phenotype. Lymphocytes in the thymoma with differentiated epithelial cells expressed a mature thymocyte phenotype. Thus, in thymomas of varying histologic types, phenotypic abnormalities of thymic epithelium are present; these phenotypic abnormalities may reflect abnormal thymic epithelial maturation.

Adult↗

Tracheal morphogenesis and fetal development of the mucociliary epithelium of the rat.

In the rat, tracheal development begins at mid-gestation (Day 11) with the formation of the tracheal groove, a longitudinal diverticulum of endodermal epithelium that evaginates from the floor of the pharynx and tubular foregut. At this stage the tracheal groove and developing foregut share a common lumen. Paired primary bronchial buds (lung buds), surrounded by lung bud mesenchyme (splanchnic mesoderm), arise from the caudal end of the tracheal groove. The formation of a longitudinal tracheoesophageal septum divides the combined tracheal groove and developing foregut into two structures, the trachea and esophagus. The trachea and esophagus grow apart, surrounded by independently organized populations of mesenchymal cells. Near this time (Day 12-13), the primary bronchial buds give rise to secondary (lobar) buds of pulmonary epithelium. This establishes the lobar pattern of the right and left lungs and marks the formation of extrapulmonary bronchi. The development of smooth muscle and cartilage within the tracheal mesenchyme precedes the differentiation of the mucociliary epithelium. Smooth muscle forms transversely oriented fascicles in the dorsal tracheal wall (pars membranacea), while pre-cartilage rings surround the remaining ventral and lateral walls (pars cartilagina). Epithelial differentiation is first evident at Day 17, with the formation of ciliated cells in the epithelium of the pars membranacea. Differentiation in the pars cartilagina trails development in the dorsal epithelium. Cell surface characteristics of the tracheal epithelium indicate that secretory cells differentiate about Day 19-20. The precise time and sequence of differentiation of mature cell types of the tracheal epithelium is yet to be determined. It is clear, however, that the development of the mucociliary epithelium in the rat is not completed at birth, but continues into the neonatal period.

Animals↗

Effect of epidermal growth factor on secondary palatal epithelium in vitro: tissue isolation and recombination studies.

Previous studies have shown that epidermal growth factor (EGF), a peptide of M.W. 6045, can specifically inhibit in organ culture the cessation of DNA synthesis and programmed cell death that normally occur in the presumptive fusion zone (PFZ) of the secondary palatal epithelium. The aim of this study was to determine if EGF acts directly on the epithelium to exert its effect and if there is a requirement for the underlying mesenchyme. Palatal processes from 13- and 14-day Swiss Webster embryonic mice were enzymatically separated into epithelium and mesenchyme which were then cultured alone or in transfilter recombination for up to 72 h. Tissues were examined by transmission- and scanning-electron microscopy and DNA synthesis was monitored autoradiographically using [3H]thymidine incorporation: In isolated epithelium cultured in control medium, cell death occurred in the PFZ and DNA synthesis did not occur in the oral and nasal epithelial regions. EGF (20-50 ng/ml) did not prevent cell death in the PFZ and failed to stimulate DNA synthesis in the isolated epithelium; EGF, however, did have an effect on epithelial cell morphology. In the presence of mesenchyme and EGF, there was extensive proliferation in the entire epithelium and cell death within the PFZ was not evident. The results indicate that the stimulation of DNA synthesis in the palatal epithelium by EGF requires the presence of the underlying mesenchyme and that EGF alone is not sufficient to inhibit programmed cell death within the PFZ of the isolated palatal epithelium.

Animals↗

Regional variation in respiratory epithelium of the nasal cavity of the bandicoot (Isoodon macrourus).

The non-olfactory ciliated epithelium of the nasal cavity was investigated in the bandicoot (Isoodon macrourus), a small ground-dwelling marsupial. Two distinct epithelial types were identified and designated conchal and septal. Conchal epithelium is non-secretory. It covers most of the naso- and maxilloturbinates, the lateral nasal wall, and part of the maxillary sinus. Septal epithelium contains mucus-secreting goblet cells. Rostrally, it covers the nasal septum and mid-ventral floor of the nasal cavity. Further caudally it lies on the ventral part of the septum and ventrally facing parts of naso- and ethmoturbinates. It corresponds closely to most published descriptions of respiratory epithelium. Ciliated and basal cells are common to both types. Conchal epithelium has a nonciliated domed cell with a rounded surface projecting into the ciliary border. This epithelium has a rich innervation and axon terminals are frequent almost to the cell surface. Septal epithelium contains goblet cells whose appearance varies according to secretory activity, and two rarer cells of unknown function, brush and pale cells, which are also seen in the olfactory epithelium of the bandicoot.

Animals↗

[Structure of the follicular epithelium of the gonads Neva lamprey Lampetra fluviatilis (classification of the follicular epithelia of vertebrates)].

During its fluvial life, the ovarian follicular epithelium of Lampetra fluviatilis undergoes polarity formation--in the animal hemisphere the follicular epithelium is flattened, in the vegetative--it undergoes a secretory specialization: as the secrete is accumulating, the follicular cells increase in volume and height, acquiring a cubical form. In connection with monotonous or differentiating morpho-physiological alterations of follicular epithelium within a single follicle during the period of rapid oocytic growth, it is suggested to widen the idea on kinds of its secondary transformation in the vertebrates. It is suggested to differ: 1) common secondary transformation, when secondary flattening (for example, in birds) or secondary specialization (for example, in fish demersal roe) embraces the whole epithelium of the follicle. In case of common secretory specialization, it can be a) isomorphous--at identical convertion of the epithelium in the whole follicle (for example, in sheatfish), b) dimorphous--when there is a certain difference in the character and degree of secretory specialization of the follicular epithelium in various follicular areas (for example in Myxine glutinosa); 2) unipolar secondary transformation when the follicular epithelium undergoes secondary flattening or secretory specialization only in the area adjacent to one of the oocyte poles (for example, in Lametra fluviatilis and Blennis follis). Follicular epithelium of the lamprey testis, unlike in other Anamnia, does not form spermatocysts; implantation of spermatids and spermia into cytoplasm of the follicular cells is not observed. Thus, histological structure of Cyclostomata testis is at a lower stage of development than in other Anamnia.

Animals↗

The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance.

Material from 25 human palatine tonsils was studied by light microscopy, immunocytochemistry, scanning and transmission electron microscopy. Special attention was focused on the structure of the epithelium lining the tonsillar crypts in the context of its ascribed immunological functions. This epithelium was not uniform and contained patches of stratified squamous nonkeratinising epithelium and patches of reticulated sponge-like epithelium. The degree of reticulation of the epithelial cells and the infiltration of nonepithelial cells varied. Reticulated patches were associated with disruptions in the continuity of basement membrane, and often also with desquamation of the upper cell layers, and contained numerous small blood vessels. The epithelial cells showed considerable variation in their morphology when surrounded by infiltrating cells. The rearrangement of their cytoskeleton and redistribution of desmosomal contacts indicate the responsiveness and dynamic nature of such epithelium. Cytoplasmic glycogen granules, located in the upper strata, suggest the possibility of energy-demanding functions such as absorption and secretion. The numerous membrane-coating granules may have contributed to cell membrane thickening and possibly also to tonsillar mucosal protection. Some areas contained a few keratohyalin granules but there was little evidence of keratinisation. The presence, and sometimes the predominance, of nonepithelial cells was characteristic of the reticulated epithelium. T and B cells often infiltrated the whole epithelial thickness, and many plasma cells were located around intraepithelial vessels, while macrophages and interdigitating cells showed a patchy distribution. It is proposed that the major functions of the reticulated epithelium are: (1) to provide a favourable environment for the intimate contact between the effector cells of immune responses; (2) to facilitate direct transport of antigens; (3) to synthesise the secretory component continually; and (4) to contain a pool of immunoglobulins. Thus the reticulated epithelium lining the tonsillar crypts represents a specialised compartment, important in the immunological functions of the tonsil as a whole.

Adolescent↗

Iron-induced accumulation of lipofuscin-like fluorescent pigment in the retinal pigment epithelium.

PURPOSE: One of the most prominent changes that occurs in the retinal pigment epithelium during senescence is the progressive accumulation of the autofluorescent pigment lipofuscin. Experiments were conducted to evaluate the role of nonenzymatic oxidation of photoreceptor outer segments in retinal pigment epithelium lipofuscin formation. METHODS: Albino Fischer rats were given intravitreal injections of ferrous sulfate, a catalyst that promotes nonenzymatic lipid oxidation. At 2 hours, 24 hours, and 7 days after ferrous sulfate administration, the retinas were examined with fluorescence microscopy to assess the formation of fluorescent products. At these same time intervals, organic solvent extracts of the retinas and retinal pigment epithelium-choroid complexes were prepared. The extracts were analyzed with thin layer chromatography to assay for the presence of soluble fluorophores. The ultrastructural appearances of the retinas were examined at the same time points. RESULTS: At both 2 hours and 24 hours after the ferrous sulfate treatment, the photoreceptor outer segments displayed a yellow-green fluorescence emission that was not present in untreated eyes. Associated with this in situ fluorescence were a number of blue-green emitting fluorophores in organic solvent extracts that did not correspond to any of the fluorophores extracted from the retinal pigment epithelium of old animals. One week after the ferrous sulfate treatment, the photoreceptor cells had degenerated and the retinal pigment epithelium contained large amounts of an autofluorescent pigment with a golden-yellow emission typical of lipofuscin. The iron-induced fluorophores could not be extracted from this pigment into either chloroform or dichloromethane. CONCLUSIONS: The initial fluorophores that were formed as a result of nonenzymatic oxidation of outer segment components did not appear to be the same as those responsible for retinal pigment epithelium lipofuscin fluorescence. However, after the oxidized outer segments were phagocytosed by the retinal pigment epithelium, the latter cells became filled with a yellow-emitting fluorescent pigment that was similar in its fluorescence properties to lipofuscin. These observations suggest that lipofuscin fluorophores are not direct products of nonenzymatic lipid oxidation. However, some of these oxidation products may be modified after uptake by the retinal pigment epithelium to form insoluble lipofuscin fluorophores.

Animals↗

Optics of the corneal epithelium.

BACKGROUND: The refractive effect of the corneal epithelium in relation to the cornea as a whole is relatively unknown, yet it may affect the efficacy of keratorefractive surgical procedures, most notably photorefractive keratectomy and epikeratoplasty. This article investigates the refractive effect of the epithelium on the cornea. METHODS: We measured the corneal keratometry in 10 fresh human eye-bank eyes with and without epithelium. All readings were performed at 2.0- and 3.6-millimeter diameter zones with an automated keratometer. RESULTS: When the epithelium was removed, there was an increase in corneal refractive power in every case. The mean change was +1.03 D (range, 0.55 to 1.85 D) at the central 2.0-millimeter diameter zone and +0.85 D (range, 0.29 to 1.60 D) at the 3.6-millimeter diameter zone. We also found a change in both the power and axis of astigmatism in most cases. CONCLUSIONS: The corneal epithelium plays an active role in determining the final surface power of the cornea. It accounts for an average of 1.03 D of the power of the eye at the central 2-millimeter diameter zone. The difference in astigmatism suggests that the epithelium does not form a layer of uniform thickness over Bowman's layer. It appears that the epithelium attempts to minimize abrupt changes in surface contour. These findings suggest that in refractive procedures such as photorefractive keratectomy the refractive contribution of the epithelium must be taken into account to improve predictability.

Astigmatism↗

Metallothionein shows an age-related decrease in human macular retinal pigment epithelium.

PURPOSE: To investigate the possible role of zinc-metallothionein in human retinal pigment epithelium with regard to age-related changes. METHODS: A cadmium/heme assay was used to quantitate metallothionein in isolated macular and peripheral retinal pigment epithelium from donors ranging in age from 28 to 91 yr (n = 16, mean age = 68.6 yr). RESULTS: It was found that peripheral retinal pigment epithelium contained significantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 +/- 2.2 micrograms metallothionein/mg cytosolic protein in donors younger than 70 yr, compared to 5.6 +/- 0.9 in macular retinal pigment epithelium from donors older than 70 yr, a 68% decline (P = 0.0007). In cultured retinal pigment epithelium, when we lowered the zinc concentration in the medium, metallothionein was reduced by 72% after 1 wk of incubation. CONCLUSIONS: It is suggested that lower levels of metallothionein in retinal pigment epithelium are caused by reduced metallothionein gene activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc.

Adult↗

Detection of trisomy 7 in nonmalignant bronchial epithelium from lung cancer patients and individuals at risk for lung cancer.

Early identification and subsequent intervention are needed to decrease the high mortality rate associated with lung cancer. The examination of bronchial epithelium for genetic changes could be a valuable approach to identify individuals at greatest risk. The purpose of this investigation was to assay cells recovered from nonmalignant bronchial epithelium by fluorescence in situ hybridization for trisomy of chromosome 7, an alteration common in non-small cell lung cancer. Bronchial epithelium was collected during bronchoscopy from 16 cigarette smokers undergoing clinical evaluation for possible lung cancer and from seven individuals with a prior history of underground uranium mining. Normal bronchial epithelium was obtained from individuals without a prior history of smoking (never smokers). Bronchial cells were collected from a segmental bronchus in up to four different lung lobes for cytology and tissue culture. Twelve of 16 smokers were diagnosed with lung cancer. Cytological changes found in bronchial epithelium included squamous metaplasia, hyperplasia, and atypical glandular cells. These changes were present in 33, 12, and 47% of sites from lung cancer patients, smokers, and former uranium miners, respectively. Less than 10% of cells recovered from the diagnostic brush had cytological changes, and in several cases, these changes were present within different lobes from the same patient. Background frequencies for trisomy 7 were 1.4 +/- 0.3% in bronchial epithelial cells from never smokers. Eighteen of 42 bronchial sites from lung cancer patients showed significantly elevated frequencies of trisomy 7 compared to never smoker controls. Six of the sites positive for trisomy 7 also contained cytological abnormalities. Trisomy 7 was found in six of seven patients diagnosed with squamous cell carcinoma, one of one patient with adenosquamous cell carcinoma, but in only one of four patients with adenocarcinoma. A significant increase in trisomy 7 frequency was detected in cytologically normal bronchial epithelium collected from four sites in one cancer-free smoker, whereas epithelium from the other smokers did not contain this chromosome abnormality. Finally, trisomy 7 was observed in almost half of the former uranium miners; three of seven sites positive for trisomy 7 also exhibited hyperplasia. Two of the former uranium miners who were positive for trisomy 7 developed squamous cell carcinoma 2 years after collection of bronchial cells. To determine whether the increased frequency of trisomy 7 reflects generalized aneuploidy or specific chromosomal duplication, a subgroup of samples was evaluated for trisomy of chromosome 2; the frequency was not elevated in any of the cases as compared with controls. The studies described in this report are the first to detect and quantify the presence of trisomy 7 in subjects at risk for lung cancer. These results also demonstrate the ability to detect genetic changes in cytologically normal cells, suggesting that molecular analyses may enhance the power for detecting premalignant changes in bronchial epithelium in high-risk individuals.

Aged↗

Unique features of the basal cells of human prostate epithelium.

The prostate gland is globally composed of epithelium and stroma. The epithelium plays an important role in the development of both benign and malignant disorders while the stroma is involved in benign prostatic hyperplasia. While the prostatic epithelium of the majority of laboratory animals is well recognized as a pseudostratified columnar, the classification of the human prostatic epithelium is controversial. Moreover, the role of the basal cells of the human prostatic epithelium is still uncertain. These cells have been described as undifferentiated cells, precursors of luminal cells, reserve and myoepithelial cells. The objective of the present study was to assess the similarities and/or differences between the epithelium of the human prostate and that of other laboratory animals and thus derive information about the potential functions of basal cells in the human prostate. In the human, basal cells form a continuous layer of cells resting on the basement membrane and upon which rests a layer of luminal cells. This results in a stratified columnar epithelium of two layers of cells, unlike the sporadic appearance of basal cells observed in other species where it results in a pseudostratified epithelium. In addition, the ratio of basal to luminal cells in the human is about 1:1, while the average ratio in the other animal species examined is about 1:7. Furthermore, the gap junctional proteins connexin 26 and 43, are present between basal and luminal cells in the human, thus suggesting that these cells communicate directly with each other. In addition, the ultrastructure of the human basal cells shows morphological evidence of differentiated but not of undifferentiated cells. Moreover, the presence of junction-like structures between adjacent basal cells suggests that these cells form a blood-prostate barrier. In this way, basal cells could prevent substances derived from the blood from directly coming in contact with the luminal cells. Human basal cells could thus regulate functions of the luminal cells by being part of a two-cell mechanism somewhat analogous to thecal and granulosa cells in the ovary.

Animals↗