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PubMed1998

Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation.

An analysis of 77 uterine endometrioid carcinomas was performed to compare pure endometrioid carcinomas and endometrioid carcinomas with various types of cellular differentiation for the expression of estrogen (ER) and progesterone (PR) receptors, p53, and Ki-67 and to correlate these findings with clinicopathologic features. Forty-three pure endometrioid carcinomas and 34 endometrioid carcinomas displaying additional types of cellular differentiation in at least 10% of the tumor (16 squamous, 11 mucinous, four ciliated cell, and three secretory) were analyzed. In 8 of the 16 tumors with squamous differentiation, the squamous component was histologically benign (low grade), and in eight tumors it was histologically malignant (high grade). In tumors showing various types of cellular differentiation except those with a high-grade squamous component, comparison of the endometrioid glandular component with the squamous, mucinous, secretory, and ciliated cell components showed that ER/PR, Ki-67, and p53 expression were generally higher in the glandular component compared with the various differentiated components. These findings parallel the changes that occur in the endometrium in the secretory phase of the menstrual cycle and, therefore, suggest that the differentiated components have undergone terminal differentiation. In contrast, in endometrioid carcinomas with a high-grade squamous component, Ki-67 and p53 expression were the same in the glandular and squamous components suggesting that squamous epithelium in these tumors represented another pathway of cellular differentiation but not one that was terminally differentiated. Endometrioid carcinomas with a high-grade squamous component had significantly higher grade (P = .002), stage (P < .001), cellular proliferation index (P = .0005), and worse outcome (P = .0009) compared with tumors with the other types of cellular differentiation, including those with a low-grade squamous component and pure low-grade endometrioid carcinomas. In addition, carcinomas with a high-grade squamous component occurred in older women and were more frequently associated with atrophic endometrium and less replacement hormone therapy, but the differences were not statistically significant. In conclusion, endometrioid carcinomas with various types of cellular differentiation can be broadly divided into two groups. Tumors with mucinous, secretory, and ciliated cell differentiation and those with a low-grade squamous component are similar to pure low-grade endometrioid carcinomas in that most have high ER and PR expression, low cellular proliferation indices, low p53 immunoreactivity, and good prognosis. In contrast, endometrioid carcinomas with a high-grade squamous component lack expression of ER and PR, have high cellular proliferation indices, often express p53, and have a prognosis similar to poorly differentiated endometrioid carcinomas.

Adult↗
PubMed2003

Centrin4p, a novel mammalian centrin specifically expressed in ciliated cells.

Centriole assembly plays an important role in centrosome duplication during the cell cycle and is a prerequisite for cilia formation during the differentiation of ciliated cells. In spite of numerous investigations, the molecular machinery that governs centriole/basal body formation remains enigmatic. Recent reports suggest that the ubiquitously expressed mammalian centrins, centrin2p and centrin3p, could be involved in the centriole duplication process. To better understand the specific functions of these proteins, we performed a systematic search for novel mammalian centrins. We isolated a cDNA and the corresponding gene coding for a novel murine centrin, centrin4p, which is more closely related to centrin2p. Like centrin2p, centrin4p accumulates to centrioles and procentrioles when ectopically expressed in HeLa cells. However, centrin4p possesses two splice variants that do not localize to centrioles, suggesting a posttranscriptional regulation mechanism. We also observed that centrin4p does not share the same centriolar targeting properties with centrin2p and 3p, indicating that these proteins could recognize different centriolar partners. Centrin4 mRNA possesses a restricted expression profile and is only detected in brain, kidney, lung, and ovary. In brain, centrin4p is exclusively expressed in ependymal and choroidal ciliated cells where it is localized to basal bodies. Together, our present data suggest that centrin4p could be more specifically involved in basal bodies assembly or in a subsequent step of ciliogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Nasal cytology: description of a hyperchromatic supranuclear stria as a possible marker for the anatomical and functional integrity of the ciliated cell.

BACKGROUND: The aim of this study was to describe a particular intracellular hyperchromatic formation located over the nucleus of normal nasal ciliated cells. This finding, never described in literature, very rarely occurs in pathological conditions. METHODS: A nasal cytological test and mucociliary transport test were performed in a group of 24 subjects with rhinologic diseases and in a control group of 10 healthy subjects. RESULTS: The "hyperchromatic supranuclear stria" (SNS) was observed in a high percentage of normal cells (90.3%); SNS was present in very few pathological subjects (in only 6.26% of pathologic cells). CONCLUSION: We interpreted SNS as a specific marker for the anatomic and functional integrity of the ciliated cell. Therefore, the absence of SNS is considered an abnormal finding in the nasal mucosa and therefore could be useful as a "prognostic sign" of the disorders themselves and as an indication of the "therapeutic efficacy" of pharmacologic treatments, both topical and systemic.

Adolescent↗
PubMed1983

Organization of intermediate filaments in ciliated cells from quail oviduct.

When ciliated cortices were isolated from oviducts of laying quail, the demembranated cortices remained associated with the cell nucleus. The organization of the material linking the nucleus to the apical cell surface has been observed by electron microscopy in ciliated cells in situ and characterized by HRP immunocytochemistry. A well developed network of prekeratin intermediate filaments attached to the desmosomes creates a basket surrounding the nucleus. Furthermore, prekeratin filaments are associated with the striated rootlets of basal bodies.

Animals↗
PubMed1999

Gonococcal infection of human fallopian tube mucosa in organ culture: relationship of mucosal tissue TNF-alpha concentration to sloughing of ciliated cells.

BACKGROUND AND OBJECTIVES: An experimental model consisting of gonococcal infection of human fallopian tube mucosa in organ culture has proven useful in studying the molecular pathogenesis of acute gonococcal salpingitis and postsalpingitis sequelae. Gonococcal infection of human fallopian tube mucosa in organ culture results in the sloughing of ciliated epithelial cells from the mucosa. This damage to the mucosa can be quantified on fallopian tube pieces by an assay of the percent of the periphery that has ciliary activity (PPCA) remaining at specific time points after infection. Although assay of the PPCA has been quite valuable, it is labor-intensive, somewhat subjective, and requires that the observers have training and experience. A more practical assay for genital mucosal damage is desirable for further investigations that employ the fallopian tube experimental model. Gonococcal infection of fallopian tube mucosa in organ culture also results in the production of easily quantified tumor necrosis factor-alpha (TNF-alpha) by the mucosa. Furthermore, treatment of the organ cultures with recombinant human TNF-alpha (rHuTNFalpha) alone also causes sloughing of ciliated cells from the mucosa. These findings strongly suggest that TNF-alpha is a mediator of the mucosal damage that attends gonococcal infection. GOALS OF THE STUDY: To determine: (1) whether the PPCA values and the TNF-alpha concentrations in fallopian tube mucosal tissues correlate closely enough to allow prediction of the PPCA from a measurement of the mucosal tissue TNF-alpha concentration; and (2) whether the correlation of the TNF-alpha mucosal tissue concentration with the sloughing of ciliated cells (measured by the PPCA) supports the hypothesis that induction of TNF-alpha by gonococcal infection, with resultant sloughing of ciliated cells, is likely to be a major pathogenic mechanism of gonococcal salpingitis and might mediate postsalpingitis infertility and ectopic pregnancy. STUDY DESIGN: A metaanalysis was performed on studies from three research groups (two laboratories in the United States and one in the United Kingdom, using identical techniques for quantifying the PPCA, TNF-alpha, or both. RESULTS: There was a close and statistically significant correlation between the TNF-alpha mucosal tissue concentration and the proportion of ciliated cells lost from the mucosa as measured by the PPCA (r = 0.95, p < 0.001). Therefore, as the mucosal tissue concentration of endogenous TNF-alpha increased, the loss of ciliated cells from the epithelium increased proportionately. CONCLUSIONS: During gonococcal infection of human fallopian tube mucosa in organ culture, the mucosal tissue concentration of TNF-alpha can be used to predict the PPCA, and therefore, the extent of mucosal damage. This finding should facilitate studies of the molecular pathogenesis of infectious diseases involving human genital mucosa. Further, the close correlation of mucosal TNF-alpha concentration with genital mucosal damage, evaluated by the PPCA, supports the hypothesis that induction of the proinflammatory cytokine, TNF-alpha, by gonococcal infection, with resultant inflammation and sloughing of ciliated cells, is an important pathogenic mechanism of gonococcal salpingitis and may mediate postsalpingitis infertility and ectopic pregnancy as well.

Cilia↗
PubMed1992

Immunodetection of annexins 1 and 2 in ciliated cells from quail oviduct.

Annexins 1 and 2 are Ca(2+)-binding proteins related to the cytoskeletal proteins which have been reported to bind in a calcium-dependent manner of F-actin and phospholipids in vitro. Proteins immunologically related to the brain 37-kDa annexin 1 and 36-kDa annexin 2 were characterized by immunoblotting epithelial ciliated cells from quail oviduct. They were detected by immunofluorescence in ciliated as well as glandular cells, using antisera and purified antibodies directed against pig brain annexins. The pattern of labeling was found in the apical part of both cell types, with close membrane association. However, a wider distribution was observed in mature ciliated cells: annexins were localized in the well developed cytoskeletal meshwork in which the ciliary apparatus is tightly anchored. After immunogold labeling, annexins 1 and 2 were located in the same area as spectrin 240/235 and at the connection sites of F-actin; both these cytoskeletals proteins were associated with the appendages of the basal body. In contrast, annexins were not detected in immature epithelial cells, while actin and spectrin were present. During ciliogenesis, the staining gradually appeared associated with the lateral and apical membranes. In this cellular model, the annexins may function during exocytosis in gland epithelial cells, where a close cytoskeleton-membrane association is observed; moreover, in ciliated cells, a relationship between cytoskeletal elements of the terminal web and annexins may exist.

Animals↗
PubMed1987

The origin of ciliated cell cysts of the anterior pituitary. An experimental study in the rat.

Rats were decapitated and the heads were stored at 4 degrees C for 24 h. The anterior pituitaries were then removed and incubated for 5 days. On the 1st, 3rd and 5th days of incubation, explants were studied by electron microscopy and immunohistochemistry using antiserum against S-100 protein. In the explant many granulated cells underwent necrosis; folliculo-stellate (FS) cells formed many cyst-like structures (CLSs) and became squamous epithelioid cells (CLS-forming cells). After incubation for 5 days the explants were isotransplanted under the renal capsules of male rats in order to observe morphological changes in the CLSs. Immediately after transplantation, the CLSs were encircled by a basement membrane, but from the 8th to 14th day, ciliation occurred in CLS-forming cells and "ciliated cell cysts" were formed. The ciliated cells were immunostained with antiserum against S-100 protein. The present study suggests that FS cells are related to CLS formation and have the potential to trans-differentiate to ciliated cells.

Animals↗
PubMed1993

Ciliated cell damage in the bronchial epithelium of asthmatics and non-asthmatics.

The importance of bronchial epithelial shedding in the pathogenesis of asthma has been highlighted by many investigators as a potential mechanism for bronchial hyperresponsiveness. It has been suggested that this disruption is the result of cytotoxic injury leading to shedding of damaged cells. To investigate whether damaged ciliated epithelial cells can be detected within the bronchial mucosa, we used tannic acid which only permeates disrupted cellular membranes, as a marker of cell damage. Bronchial biopsies from seven asthmatic and six normal subjects, were processed in tannic acid prior to preparation and sectioning for electronmicroscopic examination. Ciliated epithelial cells staining darkly with tannic acid were seen to comprise a similar proportion of the intact portion of bronchial epithelium in both normals and asthmatics (medians 31% vs 40%). We suggest that ciliated epithelial cells are not shed from the bronchial mucosa immediately after damage and that mechanisms other than granulocyte-mediated cytotoxicity may account for epithelial disruption in asthma, possibly involving the selective damage or reduced expression of intraepithelial intercellular adhesion molecules.

Adult↗
PubMed1989

Stimulus-response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+].

Changes of cytosolic [Ca2+] have been proposed to couple stimulation of ciliary movement, however, quantitative measurements of fluctuations of intracellular free [Ca2+] associated with stimulation of ciliated cells have not been investigated. In primary cultures of rabbit oviductal ciliated cells, the stimulation of ciliary activity produced by micromolar concentrations of adenosine triphosphate (ATP) and prostaglandin F2 alpha (PGF2 alpha) was associated with a transient increase of intracellular [Ca2+]. Whereas the increase of cytosolic [Ca2+] and beat frequency produced by ATP were inhibited by the Ca-channel blocker LaCl3, the rise of cytosolic [Ca2+] and frequency of ciliary beat produced by PGF2 alpha was not affected by LaCl3. These results are the first direct demonstration that fluctuations of cytosolic [Ca2+] are associated with increased ciliary beat frequency in mammalian epithelial cells. The present findings suggest two different calcium-dependent mechanisms for stimulus-coupling in ciliary epithelium: ATP acting via purinergic receptor coupled to transmembrane influx of Ca2+, and PGF2 alpha acting via receptor-mediated release of intracellular sequestered Ca.

Adenosine Triphosphate↗
PubMed1981

Effects of expectorants on the canine tracheal ciliated cells.

Many expectorants are clinically effective as they reduce viscosity and facilitate expectoration. There are, however, few reports on effects of expectorants on tracheal ciliated cells. We investigated the effects of N-acetylcysteine, ethylcysteine and bromhexine on the ciliary activities of the canine trachea. Ciliary movement was estimated using a phototransistor, and intracellular electrical activity was measured with a microelectrode method, in vitro. N-Acetylcysteine, ethylcysteine and bromhexine in low concentrations under a low perfusion rate (0.1 ml/min) produced an increase in the amplitude and frequency of ciliary beating, while N-acetylcysteine and ethylcysteine caused a cilio-depression in high concentration. N-Acetylcysteine, ethylcysteine and bromhexine, under a low perfusion rate, did not affect the intracellular electrical activity. On the other hand, these three drugs under a high perfusion rate (1 ml/min) produced no change in the ciliary movement and the intracellular electrical activity in concentrations of 10(-8)-10(-4) M. These results suggest that the increase in ciliary activity produced by the mucolytic drugs is not due to a direct effect on the ciliated cells, but rather to a mucolytic effect on the mucus around the cilia.

Acetylcholine↗
PubMed2002

Mouse strain modulates the role of the ciliated cell in acute tracheobronchial airway injury-distal airways.

Understanding cellular repair mechanisms in vivo has been advanced through the use of well-defined injury and repair models and their application to knockout and transgenic animals, primarily mice generated in a variety of background strains. However, little is known concerning the effect that mouse strain itself has on the interpretation and comparability of observations when the strain used for genetic manipulation is not the strain used to develop the model. We compared acute bronchiolar injury and repair in three strains of mice used in knockout mouse development (C57BL/6, 129/TerSv, and 129/SvEv) to the model strain (Swiss Webster) after treatment with the same dose of naphthalene and sacrificed at 1, 2, 4, 7, and 14 days after treatment. Extent of Clara cell toxicity and exfoliation was identical in the distal airways of all strains. There were significant strain-related differences in ciliated cell squamation, initiation and duration of proliferation, epithelial differentiation, and time to completion of epithelial repair. We conclude that ciliated cells play a prominent role in repair of distal airway injury, but that all phases of the repair process differ by strain. In addition, our findings reinforce that control animals must be of the same strain, ideally litter mates, when transgenic or knockout mice are used for the study of airway repair processes and mechanisms.

Acute Disease↗
PubMed1983

Nasal mucociliary transport, number of ciliated cells, and beating pattern in naturally acquired common colds.

Repeated samples of nasal epithelium were taken for in vitro study of the number and motility of ciliated cells (microphoto-oscillographic technique), and nasal mucociliary clearance transport rate was measured (saccharin test) in 26 subjects with naturally acquired common colds. The transport rate was markedly reduced during the disease, and a slight impairment remained even after 32 days. There was a considerable fall in the number of ciliated cells, and regeneration was slow. A moderate and shortlasting change in beating frequency and intracellular synchrony was also observed. It is concluded, that a common cold, as a rule, results in marked and long-lasting impairment of nasal mucociliary clearance function, and this may be the cause of some otherwise unexplainable symptoms from the nose and throat.

Adult↗
PubMed1985

Newt lung ciliated cell models: effect of MgATP on beat frequency and waveforms.

Highly coupled newt lung ciliated cell models were used to study the effects of MgATP concentration on ciliary beat frequency and waveform. Models were prepared from ciliated lung cells of the newt Taricha granulosa by trypsin dissociation of the epithelium, demembranation with Triton X-100, and reactivation with MgATP, as described previously [Weaver and Hard, 1985]. Beat frequencies were measured stroboscopically. Ciliary waveforms of reactivated models and intact mucociliary epithelial sheets were determined by single frame analysis of high-speed movies. Waveform parameters calculated included the durations of the effective and recovery strokes, the angular swings and angular velocities of the ciliary base and tip, the position of the bend along the ciliary shaft during the recovery stroke, the velocity of recovery stroke bend propagation, and the ratio of the duration of recovery stroke bend propagation to the duration of the recovery stroke itself. We found that beat frequency varied biphasically in response to MgATP at 21 degrees C, as shown previously for isolated, individual, newt lung axonemes. Apparent Fmax (maximum beat frequency) and Km values of 25 Hz and 0.14 mM, and 35 Hz and 0.47 mM, respectively, were obtained for each linear segment of the biphasic double reciprocal plot. Demembranation did not alter either ciliary waveform or the pattern of coordination. In this system, metachrony is antilaeoplectic and ciliary waveform appears to be regulated independent of beat frequency.

Animals↗
PubMed1998

Ciliated cells and chaetotaxy of the larvae of seven species of monocotylid monogeneans (Platyhelminthes) from Heron Island, Great Barrier Reef, Australia.

The distribution and the number of ciliated cells and sensilla of the oncomiracidia of seven species representing five of the six subfamilies of monocotylid monogeneans are described. The species examined include Troglocephalus rhinobatidis Young, 1967 from the Dasybatotreminae; Decacotyle floridana (Pratt, 1910) Chisholm and Whittington, 1998 from the Decacotylinae; Heterocotyle capricornesis Chisholm and Whittington, 1996 and Neoheterocotyle rhinobatidis (Young, 1967) Chisholm, 1994 from the Heterocotylinae; Merizocotyle icopae Beverley-Burton and Williams, 1989 from the Merizocotylinae; and Clemacotyle australis Young, 1967 and Monocotyle spiremae Measures, Beverley-Burton and Williams, 1990 from the Monocotylinae. The number of ciliated cells in each zone (anterior, median and haptoral) is similar between the species, but the distribution of these cells varies and generally supports the subfamilial divisions proposed for the Monocotylidae on the basis of a phylogenetic analysis of morphological characters of the adults. A silver-staining technique modified from the method of Lambert is described.

Animals↗
PubMed1986

Mechanosensitivity of cultured ciliated cells from the mammalian respiratory tract: implications for the regulation of mucociliary transport.

Mechanical stimulation of the cell surface or cilia of cultured ciliated epithelial cells derived from the rabbit tracheal mucosa resulted in a transitory ciliary beat frequency increase of 20% or more. This response was composed of a lag, rise, and recovery phase. The duration of the response, but not the maximal frequency, was increased by stronger stimulation. The ability of these ciliated cells to respond to stimulation depended on culture age; generally, cultures younger than 4 days were insensitive. The frequency response was transmitted to adjacent and more distal cells in all directions. The lag phase but not the rise time of the adjacent cell response was extended. These ciliary responses were lost when extracellular Ca2+ was removed. Replacement of Ca2+ resulted in a restoration of mechanosensitivity. In 1 mM verapamil and Ca2+ the frequency response was also lost. These results suggest that the frequency response is dependent on Ca2+ influx (although its intracellular action is unknown) and imply that mucociliary clearance is a localized self-regulating process.

Animals↗
PubMed2000

Differential expression and cellular distribution of centrin isoforms during human ciliated cell differentiation in vitro.

Centrin protein is an ubiquitously expressed cytoskeletal component and is a member of the EF-hand superfamily of calcium-binding proteins. It was first discovered in the flagellar apparatus of unicellular green algae where it is involved in contraction of Ca(2+)-sensitive structures. Centrin protein is associated with centrosome-related structures such as spindle pole body in yeast, and centriole/basal bodies in flagellar and ciliated cells. Three centrin genes have been cloned in human cells. In this work, we have performed a comparative biochemical and functional analysis of centrin isoforms using a primary culture of human nasal epithelial cells which provides an efficient way to obtain a complete ciliated cell differentiation process. RT-PCR experiments show that the expression of the three human centrin genes increases during cell differentiation, and that only centrin 2 and 3 are expressed during cell proliferation. Using polyclonal antibodies raised against recombinant human centrin 2 and 3, we show a specific pattern of protein expression. Ultrastructural immunolocalization suggests that centrin proteins are involved in the early process of centriole assembly, as they are concentrated within the precursor structures of centriole/basal bodies. It also shows a differential localisation of centrin proteins in mature centriole/basal bodies, suggesting different functions for centrins 1/2 and centrin 3. This is also supported by functional analyses showing that centrin 1 and/or centrin 2 are involved in ciliary beating.

Calcium-Binding Proteins↗
PubMed1989

Immunological detection of spectrin during differentiation and in mature ciliated cells from quail oviduct.

A protein that was immunologically related to the erythrocyte and brain alpha-240-subunit and to the brain beta-235-subunit of spectrin was characterized by immunoblotting and was detected by immunofluorescence in the apical part of ciliated cells from quail oviduct. After immunogold-labeling electron immunocytochemistry, spectrin was detected mainly in a fibrillar meshwork located between the proximal parts of the basal bodies. It was also observed to be in contact with the basal foot of basal bodies, but was not found to be associated with the apical plasma membrane. Cilia and microvilli were unlabeled. In contrast, spectrin was detected in close contact with the lateral plasma membrane of mature ciliated cells as well as in stem epithelial cells in unstimulated oviduct. During ciliogenesis induced by estrogen, spectrin gradually appeared at the apex of the cells as the apical cytoskeleton differentiated.

Animals↗