SEARCH · PubMed Health
Results for “Ciliary Motility Disorders”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A mammalian radial spokehead-like gene, RSHL1, at the myotonic dystrophy-1 locus.
Ciliary function is essential for normal cellular activity in all species from simple protozoa upwards. In humans, ciliary dysmotility or complete immobility have been identified in autosomal recessive multisystemic diseases characterized by recurrent respiratory tract infections and male subfertility due to impaired sperm mobility. Linkage to human chromosome 19q13.3 has been published for some families but no candidate genes have been identified. We report the first identification of a mammalian homolog of a radial spokehead-like protein, with high homology to proteins of sea urchins and the protozoan Chlamydomonas reinhardtii, at the myotonic dystrophy-1 locus (chromosome19q13.3). In the lower organisms, these proteins are important in normal ciliary or flagellar action, including that of sea urchin spermatozoa. Expression of the mammalian homolog was detected in the adult testis. We suggest that this gene, which we have called Radial Spokehead-Like 1 (RSHL1), is a candidate gene for familial primary ciliary dyskinesia.
The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency.
Toxins that slow ciliary beat are virulence determinants of bacteria that infect or invade ciliated epithelial surfaces. We have previously shown that the effect of the Pseudomonas aeruginosa toxin pyocyanin on ciliary beat is associated with a fall in intracellular cAMP and ATP. We have now investigated whether reduction in intracellular adenosine nucleotides might be a common mechanism of action of other bacterial toxins which slow ciliary beat. Two other P. aeruginosa toxins, 1-hydroxyphenazine (1-HP) and rhamnolipid, and two Haemophilus influenzae fractions produced by gel filtration of broth cultures were tested. The effect on human nasal epithelium ciliary beat frequency (CBF), and intracellular cAMP and ATP were measured, and the effect of two pharmacological agents, dibutyryl cAMP and salmeterol, on these changes was assessed. 1-HP, rhamnolipid and the two H. influenzae fractions slowed CBF before there was significant release of lactate dehydrogenase from the cells. The toxins also caused a fall in intracellular cAMP and ATP. Dibutyryl cAMP and salmeterol at the concentrations used do not increase baseline CBF, but diminished the fall in CBF and intracellular adenosine nucleotides. The cAMP and ATP levels in these studies were combined with those previously obtained with pyocyanin. there was a good correlation between cAMP and ATP levels and CBF. Bacterial toxins which slow CBF may act by causing a fall in intracellular adenosine nucleotides, and agents which stimulate cAMP may prevent toxin-induced slowing of ciliary beat.
Short nasal respiratory cilia and impaired mucociliary function.
A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities.
Ciliary orientation in the "immotile cilia" syndrome.
Ciliary orientation was studied in 43 patients with the "immotile cilia" syndrome. Twenty-four of these patients had total situs inversus. One mucosal specimen was taken from uterine cervical epithelium, 2 were from bronchial mucosa and 40 from nasal mucosa. The orientation of the cilia was measured from micrographs using a semiautomatic image analyzer (IBAS I). The results from patients were compared with those of 10 control subjects. The mean standard deviation and its standard deviation of the angles of ciliary orientation was 39.7 degrees +/- 9.2 degrees in 43 patients and 27.4 degrees +/- 4.3 degrees in the control group. The difference between the groups is highly significant statistically (P less than or equal to 0.001). However, there were no statistically significant differences in the standard deviations of ciliary orientation between the fields sectioned near the cell membrane or near the ciliary tip. We were also unable to find any significant differences in the standard deviations of the ciliary angles in the specimens taken from brush biopsies and excisional biopsies. There were also no statistically significant differences between the standard deviations of the ciliary angles for the groups with or without situs inversus. If 35 degrees is considered to be the limit value for the mean standard deviation between normal and pathological specimens in our total material, this would give a specificity of 0.90 and a sensitivity of 0.72.
A family with RP3 type of X-linked retinitis pigmentosa: an association with ciliary abnormalities.
The results of linkage analysis in a family with X-linked retinitis pigmentosa (XLRP) are presented. Probe M27B (DXS255), localized to Xp11.22, was only loosely linked to XLRP, whereas pHOC3 (OTC), in the more distal Xp21.1 region, was tightly linked. In this family, the conditional probability of an RP3 locus (in Xp21.1-p11.4) was found to be 0.978 compared with 0.021 for an RP2 locus (in Xp11.4-p11.2). Risk assessment showed that 2 out of 4 "at risk" females showing no clinical abnormality have a high probability of being genetic carriers of XLRP. Some affected males have recurrent respiratory infections as a result of a condition indistinguishable from the immotile cilia syndrome; indeed, there is an association between XLRP and susceptibility to respiratory infections in the majority of affected males. The possibility that previously observed ciliary abnormalities in XLRP patients might be associated specifically with an RP3 locus abnormality is discussed.
Immunohistochemical analysis of rat and human respiratory cilia with anti-dynein antibody: comparison between normal cilia and pathological cilia in primary ciliary dyskinesia.
Wistar Imamichi rat and human respiratory cilia were examined with anti-dynein antibody (AD2), which is specific for sea urchin sperm flagellar dynein. AD2-labelled fresh-frozen normal rat and human cilia stained clearly by immunofluorescence and the peroxidase-antiperoxidase (PAP) technique. On immunoelectron microscopy, AD2 labelled the outer dynein arms of normal human cilia. Paraffin-embedded normal human cilia also stained by immunofluorescence, although not always clearly. Neither the cilia of WIC-Hyd male rats, an animal model of Kartagener's syndrome, nor human cilia from patients with primary ciliary dyskinesia (PCD) reacted positively by the immunofluorescence or PAP technique. Western blots of normal rat cilia yielded a single band of about 450 kDa. In conclusion, AD2 recognizes the outer arm dynein heavy chains of healthy cilia and may be useful in diagnosing and classifying PCD light microscopically especially when only paraffin-embedded specimens are available. This approach may be of potential use for better defining and classifying PCD.
The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome.
The product of the human motilin gene (MLN) has an important role in regulating gastrointestinal motility. The precise chromosomal localisation and expression of this gene are still unresolved. Here, we report a detailed study assigning MLN to 6p21.3; MLN is tightly linked to the HLA-DQalpha locus. Moreover, MLN expression has been evaluated in a large series of tissues. Positive signals have been obtained for brain, bronchi and a gastrointestinal malignancy. Direct sequencing exon by exon of the codifying region, intron/exon boundaries and promoter has allowed the identification of three DNA polymorphisms, one of which corresponds to a common protein variant. The chromosomal localisation of MLN, and its expression in broncoepithelial cells suggests that this gene is involved in immotile-cilia syndrome (ICS) disease. Sequence and segregation analysis of the MLN gene carried out in two families, in which the disease locus was previously assigned to 6p21.3, exclude MLN as a candidate gene for the HLA-associated form of ICS.
Current status of nuclear medicine in chronic airflow limitation.
Radionuclide imaging, quite apart from its role in the diagnosis of pulmonary embolism, offers information about the distribution of ventilatory and perfusion abnormalities within the lung. The extent of ventilatory abnormality seen can be related to the severity of airways obstruction as assessed spirometrically, whilst abnormalities in the matching of perfusion to ventilation can be related to the severity of hypoxaemia in patients with chronic airflow limitation. Clearance of mucus from the lungs of patients with chronic mucus hypersecretion may be assessed by following the clearance rate of insoluble radioaerosol particles; by such means the relative contributions of mucociliary transport and of cough to the overall clearance can be observed. Clearance is often severely impaired in patients with airways obstruction; the radioaerosol technique can be used to determine the effects of drug or physiotherapy treatment. Chronic airflow limitation leading to hypoxaemia can be associated with pulmonary artery hypertension and right ventricular hypertrophy--this may be investigated noninvasively by a radionuclide test of right ventricular ejection fraction.
Methodologic considerations in mucociliary clearance and lung epithelial absorption measurements.
Measurements of mucociliary clearance and lung epithelial permeability are relatively simple to perform, with minimum discomfort to the subjects. Awareness of the factors influencing the outcome of these procedures will help to avoid errors and yield useful information about these two clearance mechanisms from both a physiological and a pathological point of view.
Deposition of aerosols and bronchial clearance measurements.
A special inhalative device is described for reproducible deposition patterns of radioactive aerosols to measure mucociliary and tussive clearance and to evaluate the effect of drugs on the bronchial tree. Additive actions on mucus transport exist between beta 2-agonists and theophylline, but not in combination with inhalative quaternary ammonium compounds (ipatropium and oxitropium bromide). Mucolytics are generally less effective on mucociliary clearance than beta 2-agonists and theophylline, positive, negative and nonresponders are often seen due to the different viscoelastic properties of the mucus. Mucus transport is more than mucociliary clearance. Two-phase gas/liquid movement and coughing are also important transport mechanisms for bronchial mucus. Therefore, bronchodilators enhance mucus transport by increasing airway patency, which increases total and regional air flow and improves cough clearance.
Role of disturbance of ependymal ciliary movement in development of hydrocephalus in rats.
We have developed a new in vitro method of quantitatively analyzing ciliary movement in the ependymal wall of the aqueduct in rats. An axial slice of the midbrain containing ependymal wall was placed in a culture dish filled with a culture medium containing latex beads 1 micron in diameter at a concentration of 10(7) beads/ml. The movement of the beads caused by flow of culture medium generated by the to-and-fro ciliary movement was recorded by a high speed video system attached to an inverted phase-contrast microscope. Ciliary movement was expressed by the speed of the latex beads (micron/s). Aqueductal ciliary movement in congenitally hydrocephalic HTX rats, congenitally hydrocephalic WIC-Hyd rats, and other normal rats was evaluated. The results suggest that in congenitally hydrocephalic WIC-Hyd rats the degree of hydrocephalus related strongly to the degree of ciliary dyskinesia, but in congenitally hydrocephalic HTX rats it did not. Considering this discrepancy, we attempted to see whether or not hydrocephalus was caused by artificial disturbance of ependymal ciliary movement in vivo. We found that continuous infusion of metavanadate, an inhibitor of ciliary movement, into the III ventricle of normal Sprague-Dawley rats for 7 days induced dilatation of the ventricular system. Although the question whether or not disturbance of aqueductal ependymal ciliary movement is related to the development of human congenital hydrocephalus is debatable, the results of the present in vitro and in vivo experimental investigations appear to suggest that the disturbance of ciliary movement in the aqueduct could at least be one of the factors contributing to the inducement of hydrocephalus in experimental conditions.
Effect of sulfur dioxide on mucociliary activity and ciliary beat frequency in guinea pig trachea.
The effects of 30 min exposure to sulfur dioxide on mucociliary activity (MCA) and ciliary beat frequency (CBF) were studied in 31 guinea pig tracheas. MCA was measured by recording the light reflected from ciliated mucous membranes using an infrared bar code reader. CBF of single ciliated cells obtained by brushing was measured with phase-contrast microscopy. Each tracheal sample was exposed to SO2 at concentrations ranging from 2.5 to 12.5 ppm, or to air for control purposes. MCA and CBF were measured before and immediately after gas exposure. A reduction in mean MCA of 63% (P = 0.0007) and statistically insignificant changes in CBF (P > 0.05) were recorded at concentrations of 2.5 ppm SO2. Higher SO2 concentrations caused a further impairment of MCA as well as a dose-dependent decrease in CBF (P = 0.002). A concentration of 12.5 ppm SO2 induced a decrease from baseline values of approximately 80% in mean MCA and of roughly 70% in mean CBF. This study demonstrates a dose-dependent SO2-induced decrease in MCA of guinea pig tracheas. The decrease in MCA was associated with an impairment of CBF only at SO2 concentrations higher than 5.0 ppm.
A method for standardizing cytologic sampling for the estimation of nasal ciliary activity.
A method for sampling cytological brushings of human nasal mucosa using phase-contrast microscopy is detailed and the modes for counting the ciliary beat frequency (CBF) are reviewed. To test the reproducibility of our method, we performed two sampling procedures on subsequent days on each of 19 volunteers and patients. The total volume of harvested cells, the number of beating ciliated cells, and the CBF were assessed. Since there are some differences present in subsequent cell samples, our findings indicate that it may be better to critically evaluate a single sampling procedure in order to establish a correct clinical diagnosis, especially if the number of harvested cells is small. The need to standardize methods for counting the CBF to achieve comparable results is stressed.
A method for measuring the orientation ("beat direction") of respiratory cilia.
We have created a method for measuring the orientation of cilia in the respiratory epithelium. Ciliary orientation is the direction perpendicular to the plane defined by the central tubules of the cilia and is an estimate of ciliary beat direction. Ciliary orientation can be estimated by measuring the angle between the plane defined by the central tubules and a reference line. The standard deviation of these measurements describes the variation present in the beat directions of the cilia. The reference line must be so chosen that the majority of measurements falls at about the middle of the 0 degree-180 degrees range. We tested measurements by using both a glass angle measure and a semiautomatic image analyzer (IBAS I). The latter approach was faster and more reproducible. We made our measurements of normal tissues on samples obtained from two healthy adult non-smokers. Measurements were made in four areas of each sample, with 59-110 cilia in each. The differences between the maximum and minimum angles of the ciliary orientation in the same area varied from 167.9 degrees to 85.4 degrees from the reference line. The standard deviation varied from 18.0 degrees to 35.4 degrees and we consider this to be a normal variation in ciliary orientation. Of the cilia, 57% were within a standard deviation of 20 degrees.
Activation of mucociliary function in chronic rhinitis: a placebo-controlled study.
The effect of HR-6 solutions containing adenosine triphosphate (either 0.5 or 5 mg/ml) and placebo on the symptoms of chronic rhinitis was studied in 11 patients in randomized, crossover study. The nasal mucociliary activity present in these patients was measured by a radioisotopic method and was impaired in all patients, varying from 1.4 to 5.5 mm/min with a mean of 3.2 mm/min. The duration of each treatment was 10 days, with wash-out periods of 4 days. The relief of the nasal symptoms was recorded. The active drugs on average improved nasal mucociliary activity by 1.9-2.1 mm/min against placebo (1.4 mm/min). At the end of the trial six patients preferred the active drugs for relief of nasal symptoms, none placebo and five had no preferences. The results indicate the need for long-term studies of HR-6 in patients with impaired mucociliary function.
Abnormal mucociliary function in a mucocele of the maxillary antrum.
We have examined the mucociliary function present in a mucocele of the maxillary antrum and have found certain abnormalities in the tissues studied. Our findings also indicate that the mucocele's intrinsic pathology is too complex to be improved by any conservative treatment and justifies its surgical removal.
[Significance of Haemophilus influenzae and other microorganisms for the pathogenesis and therapy of chronic respiratory infection].
The host's respiratory defence mechanisms are transformed to chronic inflammatory reactions by the persistence of microorganisms and hence inflict damage on the host's own tissues. This change primarily reduces the capability of the mucociliary defence mechanisms. Such impairment can result from modifications to the mucus's physical chemical properties after an infection, or from damage to the ciliary epithelium. Haemophilus influenzae, Pseudomonas aeruginosa and Streptococcus pneumoniae cause ciliary dyskinesia and eventually lead to the destruction of the ciliary epithelium. Encapsulated type b H. influenzae strains appear to slow down the cilia most markedly. There is a fundamental difference between acute and chronic infections. In the case of acute infections the patient's normal defence mechanisms are usually intact. In chronic infections the chronic inflammatory response to the microorganisms causes the disease to progress. In such cases treatment must be considerably more aggressive since the host's "cleansing" capability is diminished. Thus, antibiotics must be applied which can effectively penetrate the bronchial tree and which also remain stable and bioactive in the presence of beta-lactamase producing microorganisms such as H. influenzae. It is conceivable that, in the future, antibiotic therapy will have to be combined with antiphlogistic agents.