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Cilia and ciliogenesis in endometrial adenocarcinomas. An ultrastructural analysis.

Cilia in neoplastic cells were observed by electron microscopy in specimens from five of six consecutive patients with endometrial adenocarcinoma. Most cilia showed a range of defects, from misalignment and displacement of individual doublets to the absence of up to three peripheral doublets, the pattern varying from 9+2 to 6+2; the central pair of microtubules also was frequently missing. Single peripheral microtubules and displacement of the dynein arms were also observed. The high proportion of cilial defects in neoplastic cells (72%) compared with those in normal endometrium (26%), together with a broader spectrum of cilial abnormalities, suggests that the neoplastic state increases the number and range of cilial lesions.

Adenocarcinoma↗

Neutrophil function in the immotile cilia syndrome.

Patients with ICS have a microtubular abnormality of cilia, which is thought to contribute to frequency respiratory tract infections. Neutrophils have a cytoplasmic microtubular system that, if abnormal and malfunctioning, could also contribute to recurrent infections. Neutrophil function has been assessed in 14 patients with ICS and compared with that of controls. The ICS patients included those with the dynein defect, the radial spoke defect, and microtubular transposition. Cell migration in each patient has been examined under agarose and by Boyden chamber techniques. No significant abnormality was detected in random or directed migration of neutrophils. Six patients representing the three different types of abnormal cilia had more extensive studies of neutrophil function performed. These included assessments of bacterial phagocytosis and killing, lysosomal degranulation, and oxidative pathway activity. Phagocytosis and killing of Staphylococcus aureus 502A in vitro was normal. Hexose monophosphate pathway activity, tetrazolium dye reduction, and lysosomal degranulation by neutrophils at rest and during phagocytosis were similar to those of control neutrophils. Our findings suggest that an abnormality of neutrophil function does not play an important role in the respiratory infections of patients with ICS.

Adolescent↗

[Immotile cilia syndrome].

Immotile cilia syndrome was diagnosed in a 10 year-old boy presenting with Kartagener syndrome: chronic otitis, sinusitis, recurrent respiratory disease and situs inversus. Electronmicroscopic examination of biopsies of the nasal mucosa showed the lack of interne dynein arms, explaining the immotile cilia syndrome in that boy.

Child↗

[Transmission electron microscopy study of the nasal cilia].

The authors draw the attention on the existence of dyskinetic and immotile cilia in patients with chronic respiratory infections of unknown origin. The study of the ultrastructure of the ciliae is done by a transmission electron microscope. It is very important to make a difference between primary and acquired anomalies. Furthermore, the authors emphasize the importance of early diagnosis in view of a treatment.

Adult↗

Centrioles, primary cilia and calcium in the growth of Balb/c 3T3 cells.

In every mammalian cell the interphase centriole forms a primary cilium during some part of the cell cycle. Many sensory receptors are modifications of primary cilia, but a sensory role for primary cilia in mammalian cells has not been proven. Nevertheless, we have found that both growth factors and calcium ionophore (A23187) induce calcium fluxes and shortening of the primary cilium. This evidence raises the question of whether the primary cilium is involved in calcium fluxes that are necessary for growth stimulation in mammalian cells.

Animals↗

The immotile-cilia syndrome compared to other obstructive lung diseases: a clue to their pathogenesis.

Twentyfour adults, aged 19-47 years, with congenitally nonfunctioning cilia were investigated by clinical examination, radiography, spirometry, and in most cases by tracheobronchial clearance measurements and ultrastructural examination of respiratory tract cilia and/or sperm tails. They all suffered from chronic bronchitis, rhinitis and sinusitis, and most of them had bronchiectasis and a history of otitis. Most had spirometrically overt obstructive lung disease and four radiological signs of emphysema. Clinical profile, lung function and mucociliary clearance data were compared to corresponding data from samples of patients with other obstructive lung diseases. These comparisons indicate that a long-standing impairment of mucociliary clearance is of pathogenetic importance in common chronic obstructive lung disease associated with chronic bronchitis, but not in emphysema associated with severe alpha 1-antitrypsin deficiency without chronic bronchitis, and not in asthma. In cystic fibrosis and in hypogammaglobulinemia an impaired clearance is not of primary pathogenetic significance but may contribute to the development of obstructive lung disease.

Adult↗

Lung function and bronchial reactivity in six patients with immotile cilia syndrome.

Previous studies of immotile cilia syndrome have shown airway obstruction. The aim of this study was to analyse lung function in such patients before severe chronic obstruction had occurred. Spirometry, lung volumes, pulmonary resistance and static pressure volume diagram were studied in six patients (ages 21-43 years). Closing capacity, the volume of trapped gas and the slope of the alveolar plateau were determined with N2 wash-out tests. Regional ventilation was studied with a gamma camera after inhalation of 99Tcm-tagged dry aerosol. Arterial blood gases were determined at rest and during exercise. Bronchial reactivity was studied with FEV1 before and after inhalation of methacholine aerosol. Five of six patients showed a rather uniform pattern, dominated by signs of "small airway disease" seen in e.g. volumes of trapped gas and closing capacity. Those five patients had uneven ventilation scintiscans and bronchial hyperreactivity. Spirometric findings and lung mechanics were influenced by lung resection, scoliosis and by the lability of bronchial tone. Five patients had normal arterial blood gases at maximum work load. Working capacity was essentially normal in all but one patient, who had a high degree of obstruction. Immotile cilia syndrome is thus compatible with a comparatively well preserved lung function and a normal working capacity far into adult life.

Adult↗

Male and female infertility problems in the immotile-cilia syndrome.

The immotile-cilia syndrome is a heterogeneous disease. The dynein arms were missing totally or almost totally, and both spermatozoa and cilia were immotile in most cases examined by us. In other cases, the ciliary axoneme displayed other defects and the spermatozoa had motility although restricted; there was no progressive motility. Fourteen men with this syndrome were all sterile. Fifteen women had the syndrome and twelve tried to become pregnant. This had been successful (one, one, and two children) in three cases only. Thus, it appears that female fertility is also impaired in this syndrome, although not completely. No case of ectopic pregnancy has been reported.

Cilia↗

Patterns of cilia formation in the lower respiratory tract of the dog: a scanning electron microscopic study.

A scanning electron microscopic study of the distribution of ciliated cells in the tracheobronchial tree of 25 dogs whose ages ranged from four hours to six months was carried out. In newborn puppies, only the dorsal wall of the trachea was completely ciliated while the lateral and ventral walls showed patchy ciliation. This pattern of cilia formation persisted until five days of age when the whole tracheal wall was found to be completely ciliated. The bronchus of newborn puppies was uniformly poorly ciliated but almost complete ciliation was achieved by two days. Likewise, large and small bronchioles of newborn animals had few cilia and, although the number of ciliated cells had increased by two days, complete ciliation was never observed regardless of the age of the dog. No ciliated cells were found in the respiratory bronchioles of any of the 25 dogs.

Age Factors↗

Ultrastructural observations on morphogenesis of atypical cilia.

Though ultrastructural studies of bronchial epithelium both in man and in experimental animals revealed in a variety of conditions the presence of pathologically altered cilia, little is known about their genesis and significance. In this work we have described the alterations noticed in ciliary morphology during the formation of atypical cilia. A probable mechanism for their production is also proposed on the basis of our results.

Animals↗

[The sick cilia syndrome].

The incidence of bronchiectasis should decrease because of improved immunization, but certain defects would still cause the malady. Fifteen consecutive patients with bronchiectasis were examined for ciliary defects by examining the nasal mucosae with an electron microscope and measuring the clearance of technetium-99m from the lung with a gamma camera. Three patients were found to have defects. Compound cilia, disorganization of the tubular structure, vacuolization and deficient inner dynein arms were observed. In one patient a loss of cell membranes which returned to normal after 4 months, was observed. Ciliary abnormalitites can either be anatomical or physiological and 'sick cilia' should be considered as a cause of bronchiectasis.

Bronchiectasis↗

Effects of sauna-like heat stress on the respiratory tract ciliogenesis and cilia in adult male rats.

Rats were exposed daily to +85 degrees C for 10 min for 60 d; half of them were exposed to -15 degrees C for 8.5 min each time immediately after heating. Rats were sacrified in groups at intervals of 20 d. Their respiratory cilia were studied with the electron microscope. In ciliogenesis, and increase was noted in the nunmber of fibrogranular areas and basal bodies deep in the cytoplasm. In the cilium the 9+2 pattern was reduced to 8+2; electron-dense material appeared at the ciliary base of other cilia. The last two changes were reversible. Only the trachea and main bronchus were affected. The ciliary changes appeared only after heating followed by cooling at -15 degrees C; those related to ciliogenesis appeared with and without cooling at -15 degrees C. Heat seemed to be a non-specific stimulus, but the role of the systemic effects of hyperthermia must be considered.

Animals↗

Structural and functional hierarchy of eukaryotic cilia and flagella.

There are now a variety of methods to investigate the morphofunctional aspects of eukaryotic cilia and cilia. These methods are useful for investigating the basic mechanism of eukaryotic axonemal mechanochemical function and understanding the function and interaction of its components. It is clear that the complex structure of eukaryotic axoneme requires the combination of all these techniques to unravel its mystery. The compositionally simple in vitro microtubule assays are crucial in investigating the functions of different dyneins within an axoneme. However, because such assays do not include other components of the axoneme and the important mechanical feedback present in a beating axoneme, reactivation of the entire structure will continue to play a basic role in the morphofunctional study of eukaryotic axonemes.

Axons↗

[Mathematical modeling of the mechanism of cilia motion: an internal hydrodynamic drive].

A physical approach to the description of the motion mechanism of cilia based on the importance of hydrodynamical interactions between the intraciliary microstructures is proposed. The motion of the cilium model was investigated theoretically. A mechanism of synchronization of cilia beating in metachronal waves is proposed.

Biophysical Phenomena↗

A Tetrahymena orthologue of the mouse chaperonin subunit CCT gamma and its coexpression with tubulin during cilia recovery.

A Tetrahymena pyriformis gene orthologue to the mouse CCT gamma gene has been cloned and sequenced. The coding region of this gene, named TpCCT gamma, is interrupted by six introns and codes for a protein of 559 amino acid residues. This protein shares a 57.6% identity with the mouse CCT gamma protein whereas in average a 30% identity was found with CCT alpha proteins from mammalian to yeast. The expression of this gene was investigated by Northern blot hybridization in Tetrahymena exponentially growing cells and cells during cilia recovery. The TpCCT gamma gene is expressed producing a unique transcript of 2.1 kilobases. A relevant aspect of our findings is the coordinated response of TpCCT gamma and tubulin genes to cilia regeneration. TpCCT gamma and tubulin transcripts reached higher levels between 45-120 min of reciliation compared to those found in exponentially growing cells. These high levels could be the result of the increase in apparent transcription rates detected at 60 min of reciliation. We also observed that TpCCT gamma transcripts are not increased after exposure of Tetrahymena cells to a heat-shock (28-->34 degrees C). Our results seem to indicate an important role of this gene in the differentiation process of ciliogenesis.

Amino Acid Sequence↗

[A morphological study of ciliary abnormalities in patients with immotile cilia syndrome].

The present study has the aim of studying the morphological aspects of ciliary abnormalities in patients affected by immotile-dyskinetik cilia syndrome. Five patients affected by primary ciliary dyskinesia have been studied, examining by TEM the cells obtained by bronchial brushing during fiberoptic bronchoscopy. Many types of anomalies have been observed, and a morphologic classification was proposed. The frequency of abnormal cilia appears to be correlated to the severity of respiratory pathology. The morphological anomalies are not specific for this pathology.

Adult↗

A cilia-bearing cell system in the intrahepatic bile ductules of the rat.

A scanning electron microscopic investigation of the luminal surface of the intrahepatic bile ducts of the rat has been performed using tissue prepared by critical point drying. Results of these studies have demonstrated that intrahepatic bile ducts of the rat are composed of cells, the luminal surface of which contains either microvilli or numerous long cilia. It was suggested that these cilia play an important role in tissue function, particularly in the propulsion of hepatic bile.

Animals↗