Electron-lucent Cytoplasm Research Articles

Clear cell chondrosarcoma: case report and ultrastructural study

A case of clear cell chondrosarcoma in a Chinese patient is described. The clear cells showed strongly positive S-100 protein immunoreactivity. Ultrastructurally 2 types of chondroid cells were demonstrated. One type appeared more primitive with abundant electron-lucent cytoplasm and sparse organelles. The other type of cell was more differentiated with presence of microvilli and numerous dilated cisternae of endoplasmic reticulum. Previous ultrastructural studies on these lesions were reviewed and compared with the present findings.

Clear cell lymphoma: A clinicopathological study of four cases

Four cases of clear cell lymphoma were studied by means of light and electron microscopy, enzyme-histochemistry, and E- and EAC-rosette formation. On light microscopic examination the tumors were seen to be composed mainly of round, oval, or slight irregular cells with water-clear, abundant cytoplasm. The neoplastic cells has round, oval, or convoluted nuclei with fine, evenly dispersed chromatin and one or more small but distinct nucleoli. On electron microscopic examination the clear cell lymphoma were characterized by lymphoid cells with striking electron lucent cytoplasm with few organelles. According to E-rosette test and enzyme-histochemical findings, the investigators proposed that the clear cell lymphoma may be derived from T-cell lineages. Differentiated diagnoses of clear cell lymphoma from B-immunoblastic sarcoma, pleomorphic cell lymphoma, clear cell sarcoma, and clear carcinomas derived from lung, ovary, or kidney were discussed.

An Ultrastructural and Immunocytochemical Study of Gastrodermal Cell Types in Microstomum lineare (Turbellaria, Macrostomida)

AbstractThe gastrodermal cell types of Microstomum lineare (Turbellaria, Macrostomida) were studied by electron microscopy. Their immunoreactivity (IR) to bovine pancreatic peptide (BPP), FMRF‐amide and vasotocin, somatostatin, neurotensin, ACTH, CCK, bombesin, secretin, gastrin/CCK and insulin antisera was tested by light microscopic immunocytochemical methods. In addition to granular club cells and phagocytic cells, neurons and neoblasts occur in the gastroderm of this turbellarian species. This is the first observation of neurons in the gastroderm of a flatworm. Dense‐core vesicles (70–100 nm diameter), electron lucent cytoplasm and numerous Golgi complexes characterize the neurons. Unpolarized two‐way synapses, neuromuscular junctions and polarized chemical synapses can be observed in the gastroderm. Neoblasts with large nuclei and scanty cytoplasm and differentiating cells containing clusters of basal bodies occur next to the basal lamina of the gastroderm. BPP‐like, FMRF‐amide‐like and vasotocin‐like immunoreactivity is demonstrated in the gastroderm. Both BPP and FMRF‐amide IR is restricted to the basal cytoplasm of the granular club cells, while a different location for IR to vasotocin antiserum is observed. The status of the neuronal cell in the gastroderm of M. lineare is discussed in relation to endocrine (paracrine) cells and neurons in the gastroderm of invertebrates.

Ultrastructural characteristics of a pleomorphic liposarcoma. A possible involvement of myofibroblast.

A pleomorphic liposarcoma originated from the epicardial fatty tissue was studied with an electron microscope. The transmission electron microscopic examination revealed fibroblastic, myofibroblastic and primitive mesenchymal cells. Fibroblastic cells characterized by irregular nucleus with abundant heterchromatin and dilated cisternae were most frequently encountered, and the myofibroblastic cells, secondly in frequency, contained bundles of microfilaments with occasional dense bodies and outlined by discontinuous thin basal lamina. The primitive mesenchymal cells had mainly oval nucleus and electron lucent cytoplasm with poorly to moderately developed cell organellae. Some of the multinucleated giant cells relatively frequently observed revealed the aggregates of filaments with dense bodies at the cell margin. Many of them, irrespective of cell types, contained lipid droplets in the cytoplasm with various sizes. These observations suggest that a pleomorphic liposarcoma, at least a few of them, might contain not only fibroblastic, primitive mesenchymal but also myofibroblastic tumor cells with morphological varieties.

Testicular (Sertoli's cell)-like tumors of the ovary induced by N-ethyl-N-nitrosourea (ENU) in rats.

N-ethyl-N-nitrosourea (ENU) administered intraperitoneally or transplacentally to Sprague-Dawley (CD) and BD-IV (Berlin Druckrey IV) rats increased the incidence (26.6%) of an uncommon ovarian tumor with testicular characteristics compared either to controls (3.0%) or rats administered diethylnitrosamine (3.3%). The induced tumors were composed of tubular structures that resembled seminiferous tubules lined by Sertoli's-like cells. The abundant electron-lucent cytoplasm of the tumor cells contained polyribosomes, lipid bodies, and mitochondria but few additional organelles. Sertoli's cell-like tumors appeared to develop from the ovarian stroma in the hilar region of the ovary. They usually were benign and resulted in unilateral enlargement of the ovary. The mean serum concentrations of testosterone, estrone, and estradiol in selected rats with ovarian tumors were elevated above mean serum values in controls. There was not a consistent direct correlation between tumor diameter and circulating hormone level. Ethyl nitrosourea-induced ovarian tumors composed of testicular (Sertoli's-like) cells will provide a reproducible animal model to investigate the histogenesis and hormone secreting properties of this unique gonadal neoplasm.

Myoepithelial cell ultrastructure in the submandibular gland of man.

In human submandibular glands, two types of myoepithelial cells can be distinguished in serial ultrathin sections. The dark myoepithelial cell type was stellate in shape and exhibited a pronounced electron density due to numerous myofilaments with focal densities. Dark cell types accounted for the greater part (76%) of the myoepithelial cells and furthermore showed adenosine triphosphatase activity. This type of myoepithelial cell is considered to be that previously observed in mammalian salivary glands. Occasionally, desmosomes could be found between the processes of adjacent dark myoepithelial cell types, which is appropriate with respect to the strong compression of acinar or intercalated duct cells. The light myoepithelial cell type was large and ellipsoid with a few short-thick processes, and was characterized by an electron lucent cytoplasm which included scant and unevenly distributed myofilaments. Light cell types showed positive adenosine triphosphatase activity and accounted for only a small part (17%) of the myoepithelial cell number. Transitional forms between these two types were also observed. The light myoepithelial cell type may mature into the dark myoepithelial cell type by means of the transitional form. In addition, clear cells were sometimes encountered between the myoepithelial cell and the acinar or intercalated duct cells.

Uptake of 3H-glycine in the outer plexiform layer of the retina of the toad, Bufo marinus.

The uptake of 3H-glycine in the retina of the toad, Bufo marinus, was investigated by light and electron microscopical autoradiography. Uptake of 3H-glycine was very prominent in large cell bodies in the inner nuclear layer as well as in discrete clusters in both the outer plexiform layer (OPL) and the inner plexiform layer. This pattern in similar to that described for 3H-glycine-accumulating putative interplexiform cells in goldfish, frog, and Xenopus retinas. Electron microscopical autoradiography of the OPL revealed large, grain-containing varicosities which had electron-lucent cytoplasm and contained both small, agranular and large, dense-core vesicles. The varicosities made extensive en passant and spine synapses in the OPL. Definitive identification of their postsynaptic targets was not achieved. However, autoradiographic analysis with 3H-GABA uptake as well as electrophysiological evidence suggests that axons but not cell bodies or dendrites of 3H-GABA-accumulating horizontal cells (H1 cells) are postsynaptic targets of the varicosities. The presence of dense-core vesicles in the varicosities suggested co-occurrence of glycine and a biogenic amine or neuropeptide. The indirect immunofluorescence technique was used to determine whether any such substances were present in the OPL of the toad retina. However, no specific labeling was found in the OPL for any of 19 substances tested. The extensive synaptic output provided by glycine-accumulating varicosities in the toad OPL may indicate an important role of glycine in the synaptic function of the distal toad retina. We suggest that these varicosities derive from a presumably glycinergic interplexiform cell.

Ultrastructural changes in the oviductal epithelium of Merino ewes during the estrous cycle.

Isthmic and ampullary oviductal epithelia sampled from Merino ewes at days -1, 1, 3, and 10 of the estrous cycle (estrus = day 0) were studied by scanning and transmission electron microscopy after fixation by vascular perfusion. Secretory cells, ciliated cells, and lymphocytelike basal cells were observed in both isthmic and ampullary epithelium at all stages of the estrous cycle studied and their ultrastructural features were analyzed. Synthesis of lamellated secretory granules occurred in the ampullary secretory cells during the follicular and early luteal phases, and their contents were released by exocytosis into the oviductal lumen during the luteal phase. Granule release was associated with nucleated apical protrusion of these cells into the oviductal lumen. No such secretory activity was displayed by isthmic secretory cells even though a few cells contained nonlamellated granules. Apocrine release of apical vesicles and accompanying cytoplasmic material from apical protrusions of ciliated cells occurred in the isthmus around estrus but not in the ampulla. This unexpected feature has not previously been reported in any other mammal. Dendritic basal cells were distinguished in the lower part of the epithelium by their heterochromatic nuclei, electron-lucent cytoplasm, and lack of attachment zones. No migration of basal cells was observed, and their ultrastructural features were similar in the ampulla and isthmus and at all stages of the estrous cycle examined. The function of these lymphocytelike cells in the epithelium is uncertain, but the presence of phagocytic bodies and lysosomes in 20% of them may indicate a phagocytic role.

Light and electron microscopic studies on the subdural space, the subarachnoid space and the arachnoid membrane

Cranial meninges of humans were studied by electron microscopy after fixation in situ and histochemical demonstration of nicotinamide-adenine dinucleotide diaphorase within mitochondria. There was an intimate fusion between the innermost portion of the dura mater (dural border cells) and the outermost portion of the arachnoid (arachnoid barrier layer). Cranial meninges did not contain a true subdural space, when specimens were well prepared with spatial relationships preserved. If cleavage had occurred during preparation, the subdural space was artificially formed by the separation of dural border cells, because the latter showed a paucity of intercellular contacts and weak collagenous reinforcements. The arachnoid barrier layer was a squamous layer of elongated cells with numerous tonofilaments, desmosomes and tight junctions. There was a lining of junctional devices between the innermost two cell layers. There was a number of extracellular lacunae, being separated by interdigitations and containing collagen fibrils, elastins, granular material and matrix vesicles with or without psammoma bodies. The mitochondrial enzymes of this layer showed negative activity in intact specimens, but a positive one in cleaved dural border cells and arachnoid trabecular cells. An incomplete basement membrane covered the innermost aspect of this layer. The arachnoid trabecular cells generally had electron-lucent cytoplasm with a few tonofilaments. The cells beneath the arachnoid barrier layer had oval nuclei and wide cytoplasm containing numerous mitochondria. This layer was anchored by flattened or button-shaped pedicles, otherwise these cells formed an epithelial cluster. The cells lying within the subarachnoid space had elongated nuclei and cytoplasmic projections. The arachnoid trabeculae consisted of both a network of arachnoid trabecular cells and interwoven collagen fibrils. Alternating with these cells were numerous resting macrophages.

Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical, immunocytochemical and ultrastructural studies.

All stages of regeneration in hamster tracheal epithelium were studied following a denuding mechanical injury. At 1 h all the cells had sloughed from the wound site leaving a bare and sometimes disrupted basal lamina. Viable cells at the wound margins rapidly changed shape, flattened and migrated to cover the denuded lesion by 12 h. In addition, epithelial cells that remained viable demonstrated sublethal changes that included the rapid discharge of mucous granules from secretory cells, internalization of cilia by ciliated cells and evidence of heterophagy in both cell types. By 24 h a wave of epithelial cell divisions occurred, primarily by secretory cells. This produced a multilayered epidermoid metaplasia that was best developed at 48 h. The metaplastic epithelium was largely composed of cells with both secretory (mucous granules) and epidermoid (tonofilament bundles and numerous desmosomes) characteristics. The peroxidase-antiperoxidase (PAP) method demonstrated a few keratin-positive cells in the wound as early as 12 h post-wounding and keratin was demonstrated in more cells by 24 h. All cells in the metaplastic wound epithelium were keratin-positive by 48 h. Following 48 h some of the most superficial keratinized cells sloughed from the epithelium and the keratin content of the remaining cells began to decline. At 72 h pre-ciliated and pre-secretory cells were seen in the wound. Pre-ciliated cells were characterized by an abundant electron-lucent cytoplasm, large pale nucleus, filiform apical microvilli and evidence of ciliogenesis, similar to that seen during fetal development. Pre-ciliated cells often contained apical mucous granules, apparently carried over from the parent secretory cells. With the appearance of these columnar cells the normal mucociliary morphology was restored in small wounds by 120 h, but some persistent epidermoid metaplasia remained in the large wounds through 168 h post-wounding. These data provide further evidence for the important role of secretory cells in the histogenesis of epidermoid metaplasia and the regeneration of normal morphology following injury. The implications of these findings in understanding the histogenesis of other lesions in the tracheo-bronchial epithelium are discussed.

The cells with intracytoplasmic calcium-rich granules in the kidneys of salmonid fishes.

The head kidneys of salmonid fishes, which had a unique dark brown color, were examined electron microscopically and were found to have a large number of cells with round to oval intracyto-plasmic electron-dense granules (EDG; 150-450nm in diameter) in hematopoietic tissue. Most of these cells were round-shaped with a peripherally located nucleus rich in chromatin. The EDG were surrounded by membrane structure. X-ray microanalysis showed that these granules contained a large amount of calcium when compared with other electron-lucent cytoplasm. By atomic absorption study, the calcium contents of kidneys in two salmonid fishes, rainbow trout Salmo gairdnerii and coho salmon Oncorhynchus kisutch, were significantly higher (150-190μg/g-tissue) than those of liver and spleen (56-108μg/g-tissue) in the same species and those of kidneys, liver, and spleen (59-114μg/g-tissue)in carp Cyprinus carpio.

Salivary gland of the tick vector of east coast fever. IV. Cell type selectivity and host cell responses to Theileria parva

Responses of cells in the tick salivary gland to parasitism by Theileria parva were studied by electron microscopy. The gland is composed of three distinct types of acini (I, II, III) which together include ten or more different cell types. Of some 30 infected cells observed in the present study, all were E-cells of acinus III. The parasite thus exhibits a high degree of selectivity for acinus and cell type. The glandular cell invaded undergoes massive hypertrophy and accumulates glycogen deposits in its cytoplasm which may serve as an energy source for the growing intracellular parasite. As synthesis of its secretory material declines the product is packaged in progressively smaller secretory granules. The extensive arrays of endoplasmic reticulum are dismantled and eliminated in autophagic vacuoles. Excess secretory granules are also broken down by crinophagy. After 4 days, sporogony is completed and the host cell contains 30,000–50,000 sporozoites in an electron-lucent cytoplasm largely devoid of cytomembranes and secretory granules. Mitochondria are still present and normal in appearance. The loss of basophilia and secretory granules observed heretofore by light microscopy have been attributed to ingestion and destruction of host organelles by the parasite. The pallid appearance of the cytoplasm has been interpreted as a sign of impending degeneration of the host cell. In electron micrographs no ingestion of organelles by the parasite or degenerative changes were found. The host cell clearly remains viable and metabolically active throughout sporogony. The striking changes in its ultrastructure result from active elimination of organelles and inclusions by the host cell itself in response to parasitism.

Melanosomes in Paget's Disease of the Human Nipple

Paget's disease of the nipple is a distinct pathologic entity associated with intraductal and/or invasive carcinoma of the breast. Paget's change in the nipple is observed in 2.5% of breast malignancies. It is associated with progressive clinical changes corresponding to progressive microscopic infiltration of the nipple epidermis by “Paget” cells. The underlying intraductal carcinoma typically involves the lacteriferous sinuses and is often multifocal. Theories regarding the histogenesis of Paget's disease include: 1) ductal carcinoma cells migrating into the nipple epidermis; 2) melanocytes; 3) squamous cells of the nipple; and 4) keratinocytes which differentiate into glandular malignant cells. The histologic characteristics of Paget's disease include nests of large pale cells with granular cytoplasm and hyperchromatic nuclei with prominent nucleoli, in the epidermis of the nipple. The tumors may show continuity with underlying carcinoma of the lacteriferous ducts. Paget cells are characterized ultrastructurally by an electron lucent cytoplasm with numerous polyribosomes, extensive rough endoplasmic reticulum and golgi, numerous large mitochondria, lysosome-like inclusions, lipid bodies, and glycogen particles.

Ultrastructure of the pineal organ of the killifish, Fundulus heteroclitus, with special reference to the secretory function.

The pineal organ of the killifish, Fundulus heteroclitus, was investigated by electron microscopy under experimental conditions; its general and characteristic features are discussed with respect to the photosensory and secretory function. The strongly convoluted pineal epithelium is usually composed of photoreceptor, ganglion and supporting cells. In addition to the well-differentiated photosensory apparatus, the photoreceptor cell contains presumably immature dense-cored vesicles (140-220 nm in diameter) associated with a well-developed granular endoplasmic reticulum in the perinuclear region and the basal process. These dense-cored vesicles appear rather prominent in fish subjected to darkness. The ganglion cell shows the typical features of a nerve cell; granular endoplasmic reticulum, polysomes, mitochondria and Golgi apparatus are scattered in the electron-lucent cytoplasm around the spherical or oval nucleus. The dendrites of these cells divide into smaller branches and form many sensory synapses with the photoreceptor basal processes. Lipid droplets appear exclusively in the supporting cell, which also contains well-developed granular endoplasmic reticulum and Golgi apparatus. Cytoplasmic protrusions filled with compact dense-cored vesicles (90-220 nm in diameter) are found in dark-adapted fish. The origin of these cytoplasmic protrusions, however, remains unresolved. Thus, the pineal organ of the killifish contains two types of dense-cored vesicles which appear predominantly in darkness. The ultrastructural results suggest that the pineal organ of fish functions not only as a photoreceptor but also as a secretory organ.

Immuno-electron-microscopic identification of O-antigen-bearing oligodendroglial cells in vitro.

Monoclonal antibodies to cell-surface antigens of oligodendrocytes (Sommer and Schachner 1980; Schachner et al. 1980) were used to identify this cell type by immuno-electron microscopy in monolayer cultures of fetal and early postnatal mouse cerebellum. The ultrastructural features of antigen-positive cells confirm that they are immature and mature oligodendrocytes, but not neurons, astrocytes or fibroblasts or fibroblast-like cells. Type I oligodendrocytes are the immature ones with a relatively large amount of moderately electron-lucent cytoplasm, clusters of ribosomes and complex networks of rough endoplasmic reticulum. Large numbers of mitochondria and microtubules, but not intermediate-sized filaments are seen in these cells. They comprise more than 90% of all 0-antigen-positive cells. Type II cells comprise only approximately 5% of all 0-antigen-positive cells. They are characterized by a limited amount of electron-dense cytoplasm, which appears more compact and granular than in type I cells. The rough endoplasmic reticulum is distributed evenly throughout the cytoplasm. Microtubules and mitochondria are present, but more difficult to distinguish due to the compactness of the cytoplasm. Type II cells display the more mature ultrastructural features of oligodendrocytes.

Short-term induction of neoplastic nodules in the rat liver. II. Study of their development and the effects of withdrawal of 2-acetylaminofluorene.

Neoplastic liver nodules were induced by a single administration of N-nitrosodiethylamine (NDEA) and selectively stimulated to growth by 2-acetylaminofluorene (2-AAF) and partial hepatectomy to provide morphological data on very early and late stages of preneoplastic development. Presumptive preneoplastic liver cells were recognizable by light and electron microscopy by 2 days after partial hepatectomy, and they developed within 2 weeks into large, solid nodules consisting of plates of 2 or 3 cell layers thick, that compressed the surrounding non-nodular tissue. The cells showed nuclei with an enlarged nucleolus, tortuously dispersed rough endoplasmic reticulum (RER) and an electron lucent cytoplasm. These features remained present throughout the first 2 weeks of growth. During this period the initially small, distinct smooth endoplasmic reticulum areas proliferated gradually. They were associated with an increasing incidence of cytoplasmic membranes whorl formation and incidentally with annulate lamellae. After withdrawal of 2-AAF the majority of the nodules regressed resulting in slowly disappearing foci of glycogen rich cells. A relatively small number of solid nodules persisted. They were characterized by large cells with a homogeneous eosinophilic cytoplasm, enlarged cells with a homogeneous eosinophilic cytoplasm, enlarged nucleoli and dispersed RER. Because these characteristics were absent in nodular cells that had reverted to normal liver cells, it is not appropriate to consider these characteristics to represent neoplastic transformation per se.

Effect of cyproterone acetate on adenohypophysis of castrated mice.

Pituitaries from castrated male mice injected with cyproterone acetate were examined ultrastructurally. LH gonadotrophs showed two types: (a) those containing a dilated RER, a hypertrophied Golgi, and decreased granular content; and (b) those presenting an electron lucent cytoplasm and a nonhypertrophied RER. Following cyproterone acetate treatment both LH cell types showed increased RER cisternal hypertrophy and absence of Golgi membranes. In LH type (a) gonadotroph-increased granular content was noted. No detectable alterations were noted in FSH gonadotrophs following cyproterone acetate treatment. Cyproterone acetate may have stimulated the synthesis of the protein component but inhibited the incorporation of the carbohydrate moiety and LH release.

A Giant Cell with Dendritic Cell Properties in Spleens of the Anuran Amphibian Xenopus Laevis

Numerous large, mitotically active cells with abundant electron lucent cytoplasm, large hyperlobated nuclei and prominent nucleoli are found in the periphery of the splenic white pulp follicles of healthy Xenopus laevis. Like mammalian dendritic cells, these cells are located in B-lymphocyte-rich splenic follicles and have long cytoplasmic processes that are in intimate contact with adjacent lymphocytes. Some of the cytoplasmic processes extend through the Tlymphocyte-rich marginal zone into red pulp and appear to trap and transport foreign material (colloidal carbon and human IgG) from its initial site of entry in the splenic red pulp into the white pulp. In contrast to macrophages, these cells do not phagocytose large quantities of carbon. They also fail to stain for the non-specific esterase, either in a diffuse pattern characteristic for macrophages or in the punctate pattern found in most lymphoid cells in this species. In contrast to adjacent B-lymphocytes in the white pulp follicle, they do not stain for cytoplasmic Ig. Unlike T-lymphocytes, early thymectomy does not interfere with their development (1). Thus, this cell may well be a primitive follicular dendritic cell. If so, it offers insights into the function of the Xenopus spleen, and the phylogenetic origin of dendritic cells.

Anatomie comparée des racines des rhizocéphales Sacculina carcini Thompson et Loxothylacus panopei (Gissler) parasites respectifs des brachyoures Carcinus maenas (L.) et Rhithropanopeus harrisii (Gould); étude ultrastructurale des racines libres

A comparative examination of the free roots of Sacculina carcini, parasitizing Carcinus maenas, and Loxothylacus panopei, parasitizing Rhithropanopeus harrisii, shows numerous similar ultrastructural features as well as a few specific variations. Proceeding inwards from the outside, the following structures can be seen: (1) a thin and uncalcified exoskeleton with irregular processes fitted with vesicules forming a dense network and opening in the host's haemocoel; the whole may also display deep infoldings, these characters promote an important increase of the root surface; (2) subcuticular spaces sometimes particularly developed; (3) root cells that show a double aspect.In periphery, the electron-lucent cytoplasm with microtubules and free ribosomes, show apical villi which can penetrate the exoskeleton; mitochondria are abundant and possess a dense matrix with parallel cristae. Near the axis of the root, an electron-dense cytoplasm contains numerous rough-surfaced endoplasmic reticulum cisternae and large reserve inclusion bodies. Pictures of cytolysis are visible at the edge of cells. Middle lumen seem to appear after degeneration of some axial cells. Peculiarities of the described structures and their respective role in the absorption of substances, storage of reserves, or excretion of metabolites are discussed with regard to the host–parasite relationships.

The Respiratory Epithelium. VII. Epidermoid Metaplasia of Hamster Tracheal Epithelium During Regeneration Following Mechanical Injury<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

Regeneration was studied in female Syrian golden hamster tracheal epithelium. The epithelium was focally removed in vivo by scraping it with a blunt probe. At 2 hours, virtually all cells had sloughed from the injured area leaving a bare basal lamina. At 6 and 12 hours, flattened cells that migrated from adjacent uninjured epithelium partially covered the denuded basal lamina. Increased cell division did not occur at these times. Many of the simple squamous cells contained well-developed endoplasmic reticulum, Golgi apparatus, and mucous granules. Other cells resembled basal cells. At 24 hours the defect was covered by one or two layers of simple squamous cells. At that time, many of those cells were in division, and cell division was also greatly increased in mucous cells and basal cells in the uninjured epithelium distant from the defect. At 48 hours the epithelium was stratified, composed of four or five layers of polygonal to flattened cells, typical of nonkeratinizing epidermoid metaplasia. The cells contained many tonofilament bundles, a large Golgi apparatus, and many tiny mucous granules. Mitoses were seen in all cell layers. At 72 hours, the surface layer of cells was undifferentiated (indifferent cells) overlying an epithelium that otherwise retained its epidermoid character. Indifferent cells were characterized by an electron-lucent cytoplasm and a lack of tonofilament bundles, mucous granules, or cilla. Cells similar in other respects to indifferent cells were seen that possessed mucous granules or early signs of cilla formation. Some cells showed mucous granules and cilla developing in the same cell. By 96 hours, the regenerated epithelium was fully differentiated and was indistinguishable from the normal epithelium. These observations show that mucous cells have a significant role in the regenerative response. Mucous cells have a dual potential; they can undergo epidermoid metaplasia and still retain the ability to secrete mucus. The study explains the universal occurrence of mucosubstances in areas of epidermoid metaplasia and makes more understandable the previously reported fact that many bronchogenic carcinomas are combined epidermoid and adenocarcinomas. In the presence of a carcinogen, the hypothesis has been forwarded that initiation of mucous cells and basal cells occurs, which leads to malignant transformation and produces tumors that show active secretory activity and keratinization, often in the same cell.