Relationship between epithelial and connective tissues in the stomach of the frog Rana temporaria during metamorphosis: an ultrastructural study

In the course of metamorphosis of the stomach of Rana temporaria tadpoles there is a marked increase in the amount of active mesenchymal fibroblasts and extracellular matrix underlying the regenerating gastric epithelium. At the onset of metamorphosis, a thick PAS-positive basement membrane is developed around the epithelial component of the mucosa, formed by the apical, degenerating larval epithelium and the basal, regenerative epithelial cords. Under the electron microscope, a folded basement membrane is usually revealed under the apical degenerating epithelium while a compact basement membrane (up to 1-2 microns thick), forming both patches and more extensive areas, is frequently seen around the regenerative glandular cords. Cytoplasmic processes, extending from both the epithelial and mesenchymal fibroblastic cells, cross the basement membrane and make physical contact between the two cellular types. At mid-metamorphosis areas of thick PAS-positive basement membrane are still observed around the differentiating glandular outlines, before disappearing completely at late metamorphosis. The probable involvement of intertissue interactions between epithelium and connective elements in the morphogenesis, proliferation and differentiation of secondary, definitive frog stomach is discussed. Early contacts between epithelium and phagocytes, probably related to the invasion of epithelium by the phagocytic cells, have also been observed.     

American cutaneous leishmaniasis in a military training center located in Zona da Mata, Pernambuco, Brazil

In a case of infantile mucolipidosis type II (I-cell disease), storage was identified at autopsy in serous-type secretory cells in exocrine pancreas, in the tracheal and sublingual salivary glands and in the chief (zymogenic) cells of the gastric oxyntic glands, suggesting a systemic involvement of this type of secretory cells. The content of specific secretory granules was inversely proportional to the intensity of the storage process. The mucus-producing cells were not affected. The serous glandular system is a novel storage site in I-cell disease. Review of archival material in three further cases confirmed the findings.     

Failure conditions of glass filament yarns: a contribution to the valuation of carcinogenic potentials of fiber fragments

BACKGROUND: The circumanal glands of the dog are thought to be a glandular tissue, but there is some controversy as to whether they should be classified as exocrine or endocrine. In this study, we examined the nature of the circumanal glands to determine whether they should be described as exocrine, endocrine, or something else altogether. In addition, we investigated the cell degeneration in lobules of the circumanal glands in relation to the apocrine glands. METHODS: Light microscopic observations were made of paraffin sections stained with hematoxylin and eosin, and after immunohistochemical staining with antibodies against alpha-smooth muscle actin, keratin, filaggrin, and 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD). Samples were also examined by electron microscopy after fixation by aldehyde perfusion. RESULTS: The lobules of circumanal glands could be divided into two types on the basis of the presence or absence of cysts. Four layers (I-IV) were detected in the lobules with cysts. The outermost layer (layer I or the basal layer) consisted of flattened cells that contained bundles of tonofilaments and were stained immunohistochemically with the antibody against keratin. Layer II (the polyhedral or "spinous" layer) consisted of polyhedral cells that contained bundles of tonofilaments. These cells were connected to adjacent cells by desmosomes, interdigitations, and gap junctions, and they were immunopositive for keratin. A small number of polyhedral cells were immunopositive for 3beta-HSD. Layer III (the granular layer) was composed of flattened cells that contained hematoxylin-stainable granules and were moderately immunopositive for filaggrin. The innermost layer (layer IV or the horny layer) consisted of keratin. Lobules without cysts consisted only of layer I (the basal layer) and layer II (the polyhedral layer). Lobules of the circumanal glands were not directly connected to apocrine glands. Polyhedral cells degenerated and were phagocytosed by basal cells at a periphery of lobules. Then, basal cells phagocytosing degenerated polyhedral cells escaped from lobules, moved into the walls of apocrine glands, and, finally, dropped into the lumen of apocrine glands. CONCLUSIONS: Lobules of the circumanal glands have many characteristics of epidermis (a basal layer, a polyhedral or "spinous layer," a granular layer, and a horny layer) and they should not be classified as glandular tissue. The cysts in lobules can be interpreted as "closed hair canals." We suggest that steroid metabolism might occur in the polyhedral cells of the lobules.     

On strategies for comparing occupational exposure data to limits

Although research interest in the Harderian gland (HG) has increased during the last few years, only a small amount of information exists about its organogenesis. In mouse the HG appears in the posterior part of eye region, in the form of nonluminated tubules between the sixteenth and eighteenth days of gestation. At birth it is still not differentiated histologically. In birds the HG originates from the conjunctival epithelium at a late embryonic stage. In the English sparrow, Passer domesticus (incubation period of about 13 days), it appears between the seventh and the eighth days of incubation. In the chick embryo (incubation period of about 21 days) it originates between the eleventh and the twelfth days. Among reptiles the lizard Podarcis s. sicula has proved to be a useful model to clarify the embryological origin of the orbital glands since it possesses the anterior lacrimal gland contiguous to the HG in the medial corner of the orbit. The anlage of the orbital glands appears on about the twenty-second day of development (incubation period of about 43 days) in the form of a short tubule projecting from the conjunctival epithelium, at the time of development of the nictitating membrane. At this stage the mesenchymal cells surrounding the glandular blastema form a well-defined sac, later occupied by the orbital glands. From this stage until hatching the growth of the glandular blastema continues with the formation of acini which move posteriorly into the preformed mesenchymal sac. At the thirty-sixth day of development the more lateral acini differentiate into the HG. Only at the forty-first day do the more medial acini differentiate into the anterior lacrimal gland. At hatching the HG is fully differentiated. In anuran amphibia the primordium of the HG appears during the metamorphosis at the time of development of the nictitating membrane.     

Histochemical study of magellanic penguin (Spheniscus magellanicus) minor salivary glands during postnatal growth

The histological and histochemical features of the minor salivary glands during postnatal development have been generally associated with the type of food ingested. However, recent studies support the fact that these salivary glands develop independently of the diet; in fact, minor salivary glands have similar morphological and histochemical characteristics in adult individuals of species with different diet regimens. Thus, the aim of this study was to characterize the developmental morphology of the penguin minor salivary glands and to contrast them with minor salivary glands of other species. The tongue, palatine, and mouth cavity (bottom) minor salivary glands of newborn, 1- to 20-day-old, and adult magellanic penguins were studied with hematoxylin-eosin, periodic acid-Schiff, alcian blue, toluidine blue, and lectin histochemistry. Minor salivary glands were present at all ages, although they were only moderately developed in animals less than 15 days old. After this age, glands were abundant in all age groups; in addition, cells from the glandular epithelium were functionally mature and secreted mucins. Nevertheless, in newborn to 15-day-old penguins, mucins were located only at the apical cytoplasm of mucous cells. In all ages, mucous cells displayed periodic acid-Schiff-positive, alcianophilic, and metachromatic reactions; among mucous cells, other orthochromatic cells appeared interspersed. From 15 days on, histochemical reactions became more intense until adulthood, and the cytoplasm of secretory cells was filled with glycoproteins and sulfomucins. Moreover, lectins bound to different oligosaccharides in mucous cells, depending on the stage of maturation of the glands. In conclusion, penguin minor salivary glands are already present at birth, and show progressive and quantitative increases in mucous secretion during postnatal development. These changes are necessary not only for nutrient ingestion, but also for nonimmune protection of the buccal cavity.     

Expression of transforming growth factor-beta 1 messenger ribonucleic acid and the modulation of deoxyribonucleic acid synthesis by transforming growth factor-beta 1 in human endometrial cells

OBJECTIVE: The purpose of this study was (1) to evaluate the potential sites of transforming growth factor-beta 1 synthesis in human endometrium by analyzing separated endometrial glands and stromal cells for transforming growth factor-beta 1 messenger ribonucleic acid by Northern analysis of total ribonucleic acid and (2) to investigate the effects of transforming growth factor-beta 1 on deoxyribonucleic acid synthesis in endometrial epithelial and stromal cells in culture. STUDY DESIGN: Endometrial glands and stroma from proliferative and secretory endometrium were isolated after collagenase treatment of endometrial tissue minces and were analyzed for transforming growth factor-beta 1 messenger ribonucleic acid by Northern analysis. We studied the effects of estradiol-17 beta and transforming growth factor-beta 1 on deoxyribonucleic acid synthesis in endometrial epithelium and transforming growth factor-beta 1 on stromal cells in culture by evaluating tritiated thymidine incorporation into trichloroacetic acid-precipitable material. RESULTS: Transforming growth factor-beta 1 messenger ribonucleic acid was detected for Northern analysis in separated endometrial stromal cells in levels that were greatest during the secretory phase and in greater levels than in epithelial cells from that same tissue. Transforming growth factor-beta 1 messenger ribonucleic acid in glandular epithelium in culture was not increased to detectable levels by treatment with transforming growth factor-beta 1. Deoxyribonucleic acid synthesis in endometrial glandular epithelium was inhibited by transforming growth factor-beta 1, but transforming growth factor-beta 1 stimulated deoxyribonucleic acid synthesis in endometrial stromal cells in culture. After treatment for 5 days with estradiol-17 beta (10(-8) mol/L), deoxyribonucleic acid synthesis in endometrial glands in culture was decreased by 40%. Transforming growth factor-beta 1 (1 ng/ml) did not alter this effect of estradiol-17 beta on deoxyribonucleic acid synthesis. CONCLUSIONS: Transforming growth factor-beta 1 acts to decrease deoxyribonucleic acid synthesis in epithelial cells and to increase it in stromal cells isolated from human endometrium and maintained in monolayer culture. Transforming growth factor-beta 1, potentially of stromal cell origin, could participate in the regulation of endometrial cell proliferation and differentiation in vivo.     

The histologic spectrum of Barrett's esophagus

To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.     

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.     

Histological and ultrastructural observations on the development of the lung of the fetal pig

Lungs of fetal pigs having gestational ages ranging from 80 to 115 days were examined histologically and by electron microscopy. At 80 days bronchial epithelium was ciliated but bronchiolar cells were not and bronchial mucosal glands were absent. Peripheral regions consisted predominantly of mesenchymal tissue with glandular alveoli. 92 days marked the transition from the immature to the more mature lung type. Bronchial glands appeared and began to grow from the epithelium into the lamina propria, bronchiolar epithelial cells acquired cilia, and alveoli were becoming irregular in shape and had thinner interalveolar septa. Close contact between capillaries and alveolar epithelium established the blood-air barrier at many points. Differentiation of alveolar epithelium into types I and II pneumonocytes occurred at this stage and lamellated osmiophilic inclusion bodies were present in type II cells for the first time. The number of lamellated bodies increased progressively to term at 115 days.     

Gastrointestinal drugs

The cutaneous glands of the forehead and the metatarsus were studied by histological and histochemical methods and electron microscopy in adult male and female impalas in various seasons of the year. All glandular areas consist of apocrine and holocrine glands, which, however, occur in different proportions. Our findings in the apocrine gland cells suggest (1) the synthesis and exocytosis of a glycoproteinaceous secretory product stored in secretory granules, (2) typical apocrine secretion of the transformed apical cytoplasm, and (3) transepithelial fluid transport. The Golgi apparatus and apical membrane have binding sites for several lectins (PNA, HPA, RCA I, WGA). Cytokeratins 7, 14 and 19 are expressed at various intracellular localizations, suggesting an active role in the secretory mechanisms. The glands of the male forehead show marked seasonal changes in activity that are correlated with the main phases of the reproductive cycle, with the highest cellular activity occurring during the rut in April/May. The female forehead glands are only moderately developed and do not undergo seasonal changes. The metatarsal glands are of equal size in males and females and show no seasonal changes in activity. This study supports the hypothesis that (1) forehead glands in the male have a signaling role in the rut and (2) the metatarsal glands have a more general, probably social role maintaining and restoring contact between herd members.     

Temporary vehicle immobilization: evaluation of a program in Ohio

Undifferentiated glandular stomach tissue fragments from 16.5-day fetal rats were transplanted under the kidney capsule of syngeneic adult rats, and the proliferation, differentiation and morphogenesis of the transplanted tissues were investigated. Gastric epithelial cells began to invaginate 3-4 days after the transplantation and immature glands were formed after 1 week. During the period, there was a gradual increase in the expression of pepsinogen and cathepsin E, markers of cytodifferentiation of the stomach epithelia, both at protein and mRNA levels. Cathepsin E was weakly expressed in undifferentiated gastric epithelial cells at 16.5 days of gestation, and a higher level of the expression was observed in differentiated epithelia of the transplants. In contrast, the pepsinogen-producing cells first appeared around days 3-4 after transplantation and gradually increased in number to about 30% of the epithelial cells and became localized at the bottom of the gland. During the period of the experiment up to 1 month, the pepsinogen-producing cells were all positive for class III mucin and cathepsin E, indicating the immature character of these cells. In addition, no parietal cells were observed. When the tissue fragments were transplanted into adrenalectomized animals, the epithelial differentiation and morphogenesis was suppressed, but its proliferation was enhanced. The observed changes were reversed by hydrocortisone replacement. These results suggest that the development of the 16.5-day fetal stomach is regulated intrinsically to a certain extent by the genetic program of the cells involved and various gastric functions develop in the absence of luminal stimulation, stage-specific systemic hormonal change, neuronal regulation or other systemic influences, and that glucocorticoids modulate the developmental program of the fetal stomach tissues.     

Sendai virus fusion activity as modulated by target membrane components

It is generally known that the anuran stomach begins to express pepsinogens (Pg) during metamorphosis. To clarify the mechanisms of differentiation of Pg-producing cells, we examined immunohistochemically the epithelial transformation from larval to adult form in Xenopus laevis stomach at the cellular level. At the beginning of metamorphic climax, concomitantly with the modification of the basement membrane, apoptotic cells labelled by TUNEL suddenly increased in number in the entire epithelium except for the primordia of adult epithelial cells in the basal region of larval glands. Subsequently, with the development of connective tissue, the adult epithelial cells actively proliferated and replaced the larval cells from the basal to the luminal region. Following the start of morphogenesis of adult glands, Pg-producing cells became differentiated in newly formed adult glands, but not in the adult surface epithelium. We then developed an organ culture system and examined effects of thyroid hormone (TH) on the differentiation of Pg-producing cells in X. laevis stomach in vitro. In the presence of TH, just as in spontaneous metamorphosis, Pg-producing cells differentiated from the adult epithelial primordia after the apoptosis of larval epithelial cells. In contrast, in the absence of TH, neither apoptotic larval cells no Pg-producing cells were detected. Therefore, we conclude that TH triggers organ-autonomously the entire process leading to the differentiation of Pg-producing cells in X. laevis stomach. In addition, the strict localization of Pg-producing cells in the adult glands both in vivo and in vitro suggests the correlation between the differentiation of Pg-producing cells and morphogenesis of the glands surrounded by the developed connective tissue.     

Biochemical evidence that Semliki Forest virus obtains its envelope from the plasma membrane of the host cell

The data from chemical studies and electron microscopy suggest that Semliki Forest virus obtains its envelope by budding into the medium from the plasma membrane of the host cell. Biochemical evidence for this phenomenon, however, has not been published. Therefore, we undertook a series of pulse-chase studies so that we might quantitatively evaluate the importance of the budding mechanism in the morphogenesis of Semliki Forest virus. Baby hamster kidney cells (clone 13) were grown in culture and infected with Semliki Forest virus. The cells were exposed to [4,5-3H] leucine for 20 min and the subsequent incorporation of the label into virus proteins associated with cytoplasmic membranes and extracellular virus was determined. Initial experiments were conducted with microsomes and a precursor-product relationship was demonstrated between viral proteins in the microsomes and in extracellular virus. Further studies were performed with endoplasmic reticulum and plasma membrane preparations. Maximal incorporation of [3H] leucine was observed in the viral proteins located in the endoplasmic reticulum at the end of a 20-min pulse period; greater than 50% of this activity had disappeared within 2 h. The plasma membrane fraction contained no radioactivity at the end of the pulse period; subsequently, maximal labeling of the viral proteins in the plasma membrane occurred 4 h into the chase period and these labeled proteins had disappeared from this membrane 11 h after the pulse. At this time maximal incorporation of the labeled proteins into extracellular virus was observed. These data are consistent with a precursor-product relationship between the viral proteins in the endoplasmic reticulum which migrate to the plasma membrane and are subsequently incorporated into extracellular virus. All the radioactivity in the extracellular virus appears to have been derived from viral proteins associated with the plasma membrane of the cell. Therefore, mechanisms for the morphogenesis of Semliki Forest virus (in baby hamster kidney cells), other than budding from the plasma membrane, are unlikely to be of quantitative importance.     

Expression of novel potassium channels in the chick basilar papilla

Ionic currents are critical for the functioning of the inner ear auditory sensory epithelium. We set out to identify and molecularly clone the genes encoding the channels responsible for several currents in the chick basilar papilla. Here we describe an inward-rectifying K+ channel, cKir2.3, present in both hair cells and support cells in the apical end of the chick basilar papilla. The biophysical properties of the human ortholog, hKir2.3, are similar to those of an inward-rectifying channel found in the apical end of the chick basilar papilla, suggesting that this channel may contribute to the corresponding current. Additionally, we describe two new members of the Kv6 subfamily of putative regulatory voltage-gated K channels, cKv6.2 and cKv6.3. Both are expressed in hair cells in the apical end of the chick basilar papilla; cKv6.2 is also strongly expressed in support cells and in the brain.     

Dysfunctional parenting as a risk factor to lifetime depression in a sample of employed Japanese adults: evidence for the ''affectionless control'' hypothesis

A lectin histochemical study was performed to investigate the glycoconjugate saccharidic moieties on the endometrial epithelium and stroma in 12 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation for embryo transfer (IVF-ET) in early luteal phase. 7 control subjects were also evaluated. For this purpose a battery of seven horseradish peroxidase-conjugated lectins (PNA, SBA, DBA, WGA, ConA, LTA and UEA I) was used. Cytochemical controls were performed for specificity of lectin-sugar reaction. As far as the endometrial glands and stroma are concerned, the obtained data showed no differences in the endometrial lectin binding between the subjects of the control group and the ones undergoing COH, with the exception of PNA reactivity at the level of the apical portion of the glandular cells, which was detected only in COH women. It is noteworthy that, although the endometrial dating using the Noyes's criteria showed marked dissynchronies between the stroma and the glands in COH subjects, a uniformity of lectin binding, revealing the same type and localization of terminal oligosaccharides, was observed in all the examined subjects. The uniformity in distribution of the sugar residues detected in the endometrial specimens following COH might be due to the massive FSH and/or hCG treatment which probably determines an endometrial environment almost equal in all the examined subjects. In all the treated subjects reactivity with sialidase-WGA and ConA, revealing the presence of N-acetyl-D-glucosamine and D-mannose respectively, was detected at the level of the lining epithelium.     

Cell surface-associated extracellular distribution of a neural proteoglycan, 6B4 proteoglycan/phosphacan, in the olfactory epithelium, olfactory nerve, and cells migrating along the olfactory nerve in chick embryos

The immunocytochemical and immuno-electron microscopic distribution of a neural proteoglycan (PG) was investigated with a monoclonal antibody, MAb 6B4, in the olfactory epithelium, the olfactory nerve, and the cells originating the epithelium and migrating along the olfactory nerve toward the forebrain in chick embryos. The PG recognized by MAb 6B4, that is 6B4 PG, in the brain of early postnatal rats, is identical to phosphacan. In chick embryos, immunoreactivity to 6B4 PG appeared on embryonic day (ED) 3-3.5 in a thin layer beneath the olfactory epithelium. It disappeared immediately, then becoming apparent in the bundles of the olfactory nerve. The immunoreactivity in the nerve bundles gradually increased during ED 5-11. On the other hand, cell surface-associated extracellular localization of the immunoreactivity was seen in the olfactory epithelium on ED 6 and afterwards. Immunofluorescent double-labeling of 6B4 PG and gonadotropin-releasing hormone (GnRH) revealed that the cell bodies of both GnRH-containing cells and other cells migrating along the olfactory nerve were surrounded by a rim immunoreactive to the PG. Under an electron microscope, the surfaces of the cell bodies and of the neurites in the nerve bundles were surrounded by deposits immunoreactive to 6B4 PG. These results indicate that 6B4 PG in chick embryos is one type of cell surface-associated extracellular matrix molecule, and that 6B4 PG covered the surfaces of migrating cells and of elongating olfactory nerve. The cell surface-associated extracellular localization of 6B4 PG found in the nasal region, taken together with the binding properties of this PG with cell adhesion molecules shown in rat brains, suggested that 6B4 PG played a role in guiding the migration of cells along the olfactory nerve in chick embryos.     

Mesenchyme specifies epithelial differentiation in reciprocal recombinants of embryonic lung and trachea

Normal lung morphogenesis and cytodifferentiation require interactions between epithelium and mesenchyme. We have previously shown that distal lung mesenchyme (LgM) is capable of reprogramming tracheal epithelium (TrE) from day 13-14 rat fetuses to branch in a lung-like pattern and express a distal lung epithelial phenotype. In the present study, we have assessed the effects of tracheal mesenchyme (TrM) on branching and cytodifferentiation of distal lung epithelium (LgE). Tracheae and distal lung tips from day 13 rat fetuses were separated into purified epithelial and mesenchymal components, then recombined as homotypic (LgM + LgE or TrM + TrE) or heterotypic (LgM + TrE or TrM + LgE) recombinants and cultured for 5 days; unseparated lung tips and tracheae served as controls. Control lung tips, LgM + LgE, and LgM + TrE recombinants all branched in an identical pattern. Epithelial cells, including those from the induced TrE, contained abundant glycogen deposits and lamellar bodies, and expressed surfactant protein C (SP-C) mRNA. Trachea controls, and both TrM + TrE, and TrM + LgE recombinants did not branch, but instead formed cysts. The epithelium contained ciliated and mucous secretory cells; importantly, no cells containing lamellar bodies were observed, nor was SP-C mRNA detected. Mucin immunostaining showed copious production of mucous in both LgE and TrE when recombined with TrM. These results demonstrate that epithelial differentiation in the recombinants appears to be wholly dependent on the type of mesenchyme used, and that the entire respiratory epithelium has significant plasticity in eventual phenotype at this stage in development.     

Three approaches to regression analysis of receiver operating characteristic curves for continuous test results

Individual gastric glands of the stomach are composed of cells of different phenotypes. These are derived from multipotent progenitor stem cells located at the isthmus region of the gland. Previous cell lineage analyses suggest that gastric glands, as in the colon and small intestine, are invariably monoclonal by adult stages. However, little is known about the ontogenetic progression of glandular clonality in the stomach. To examine this issue, we employed an in situ cell lineage marker in female mice heterozygous for an X-linked transgene. We found that stomach glands commence development as polyclonal units, but by adulthood (6 weeks), the majority progressed to monoclonal units. Our analysis suggests that at least three progenitor cells are required to initiate the development of individual gastric glands if they are analyzed just after birth. Hence, unlike the colon and small intestine, stomachs showed a significant fraction (10-25%) of polyclonal glands at adult stages. We suggest that these glands persist from polyclonal glands present in the embryonic stomach and hypothesize that they represent a subpopulation of glands with larger numbers of self-renewing stem cells.