PubMed Health⌕ Search

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.

At least 91 records · Page 5Linked to original sources
PubMed2002

Correlation of presentation and pathologic condition in primary ciliary dyskinesia.

OBJECTIVES: To better characterize primary ciliary dyskinesia (PCD) and improve the diagnosis of this uncommon disorder. STUDY DESIGN AND SETTING: We retrospectively reviewed the records of 118 patients with ciliary biopsy or brushing specimens examined at Yale University School of Medicine from 1991 to 2001. RESULTS: Sinonasal, middle ear, and pulmonary infections were more common in patients with PCD-positive biopsy results than in those with negative results. In addition, PCD caused by random ciliary orientation presented similarly to PCD caused by other ultrastructural defects. CONCLUSIONS: Patients who present with cough alone are highly unlikely to have PCD (chi(2 ) test, 24.85; P<.001). In contrast, patients who present with multiple manifestations are highly likely to have PCD (chi(2) test, 22.2; P<.001). This information may assist the clinician in the diagnosis of PCD.

Adolescent↗
PubMed1988

[Mucociliary transport and bronchial inflammation].

The system of mucociliary clearance has the important task to remove from the airways inhaled substances and locally formed secretions. Inborn disorders of the mucociliary transport are the result of ciliary dysfunction (primary ciliary dyskinesia) or of increased viscosity of the bronchial secretions (mucoviscidosis). By far more frequency however are acquired disturbances. Inflammation of the airways results nearly always in disorder of the mucociliary transport which in early stages is reversible. With morphologic lesions, the disturbance may become irreversible. Infectious inflammations, especially those by rhinoviruses and mycoplasma, are causing ciliostatic and ciliotoxic alterations which may disturb the mucociliary clearance up to one year following the infection. Noninfectious inflammation is at first accelerating the transport of mucus through the action of cells of the body itself, especially granulocytes and eosinophiles and mediators liberated from them. Probably, these are causing a cilioexcitation which is later followed by a long-lasting depression of the mucociliary transport caused by production of mucus with high viscosity. Therapeutic measures consist in an early anti-infectious treatment and in the stimulation of the frequency of ciliary beating by beta-adrenergic drugs.

Bronchi↗
PubMed1993

Defects in cellular immunity in chronic upper airway infections are associated with immunosuppressive retroviral p15E-like proteins.

Partial defects in cell-mediated immunity have been shown in patients with chronic purulent rhinosinusitis. These defects, ie, impaired delayed-type hypersensitivity (type IV) skin reactions on commensal microorganisms of the upper respiratory tract and impaired chemotactic responsiveness of monocytes, are associated with the presence of immunosuppressive retroviral p15E-like proteins in the serum of these patients. In this study, we tested whether partial defects in cellular immunity could also be demonstrated in other groups of patients with chronic upper airway infections. Therefore, three well-characterized groups of patients with chronic upper airway infections were investigated: (1) patients with primary ciliary dyskinesia, a congenital disorder of respiratory cilia, resulting in absence of mucociliary clearance and, as a consequence, in chronic respiratory infections; (2) patients with chronic rhinosinusitis, with normally functioning cilia and with nasal polyps; and (3) patients with chronic rhinosinusitis, with normally functioning cilia but without nasal polyps. Our results show that in all three groups, most patients (87%) had defects in cellular immunity associated with the presence of p15E-like proteins in their serum. These results indicate that during chronic infections of the upper respiratory tract, immunosuppressive retroviral p15E-like proteins are found, which are probably responsible for the partial immune defects found in these patients.

Adolescent↗
PubMed1993

Do nasal ciliary changes reflect bronchial changes? An ultrastructural study.

Ciliary dyskinesia is characterized by recurrent respiratory tract infections secondary to abnormal ciliary structure and function. The diagnosis of ciliary dyskinesia is based on the detection of axonemal ultrastructural abnormalities (AUA) is respiratory mucosa samples. In most cases, the diagnosis of AUA is made on samples obtained from nasal ciliated cells with little discomfort to the patient. However, no studies have been performed in the same patient to confirm whether nasal samples reflect bronchial ciliary changes. To answer this question and to determine whether it is necessary to sample bronchial cells for the diagnosis of ciliary dyskinesia, we investigated 12 patients (between the age of 5 and 63 yr) with chronic sputum production. The presence of situs inversus, bronchiectasis, chronic sinusitis, and sterility was investigated to determine an inherited disorder. Two groups were established: Group 1 = six patients with an inherited disorder and Group 2 = six patients without evidence of an inherited disorder. Samples were obtained by brushing or biopsy of nasal and bronchial mucosa and were processed for transmission electron microscopy. In Group 1, the mean AUA was 65.2 +/- 11.4%. The following predominant axonemal defects were found: absence of dynein arms (DA) (four patients), central complex abnormalities (CC) (one patient), and various AUA (one patient). Nasal and bronchial samples correlated significantly for total AUA (r' = 1, p < 0.01) and for outer DA defects (r' = 0.96, p < 0.05). A good but not significant correlation was found for inner DA (r' = 0.83) and peripheral microtubule (PM) defects (r' = 0.71). In Group 2, the mean AUA was 9.6 +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

[Primary ciliary dyskinesia. report of three cases].

Primary ciliary dyskinesia is an autosomal recessive disorder, characterized by total or partial dysfunction of the ciliary or flagellated cells. It is clinically expressed by sinusitis and/or bronchiectasis occasionally associated with sterility in males. We report three cases of immotile cilia syndrome with chronic respiratory symptoms (sinusitis, bronchitis, otitis). The syndrome was associated with bronchiectasis in two cases and by half lobe atelectasis in the third. Diagnosis was established by ultrastructural study of samples from the nasal mucosa, in which the absence of the dynein arms and/or the anomalous disposition of the microtubules was observed. In all three patients great clinical improvement and symptom control were achieved, thereby improving the prognosis of these children. Although the syndrome cannot be cured, as in other chronic pneumopathies, early diagnosis and appropriate treatment can considerably reduce morbidity.

Bronchiectasis↗
PubMed2006

[Revision of the immobile ciliary syndrome on the ENT speciality's point of view].

Primary ciliary dyskinesia is a disorder characterized by the presence of recurrent infections of the superior and inferior respiratory tract. It is caused by a recessive autosomic genetic disorder. Its diagnosis is often given late, because other diagnostic possibilities are thought of first. It is common to find many previous visits to the ENT specialist in a medical record. The final diagnosis is given by electronic microscopy observing the ciliary defect, which is frequently due to the absence or anomalies of dineine in the arms and in the structures of the microtubule pairs responsible of movement. The mucus to study is usually obtained from the inferior nasal concha. In the rest of cases the mucus of the tracheobronchial apparatus is only studied if a fibrobronchoscopy is necesary in order to evaluate bronchial compromise or when the nasal sample is not sufficient. The ENT specialist must be alert in order to be able to think of this entity. The genetic advice is the best way to prevent it.

Ciliary Motility Disorders↗
PubMed1988

[Immotile cilia syndrome. Presentation of 3 cases].

Immotile cilia syndrome is an uncommon disorder, with an autosomal recessive mode of inheritance; the incidence is about 1/25,000 and is a cause of chronic disease of both upper and lower airways, male infertility and, in 50%, situs inversus totalis. It's pathogenesis lies in a variety of genetically determined alteration of ciliary ultrastructure. We report three cases, two in siblings, who had a typical syndrome, all of them with situs inversus totalis (Kartagener syndrome), chronic nasal symptoms, sinusitis and serous otitis with hearing loss. Two had recurrent productive cough with chest X-ray changes suggestive of bronchiectasis. The diagnosis was established in two by bronchial biopsy, showing complete and partial dynein deficiency respectively. In the third case it was based an clinical grounds and familial history. All three children are doing well up to now.

Adolescent↗
PubMed2005

Primary ciliary dyskinesia: clinical presentation, diagnosis and genetics.

Primary ciliary dyskinesia (PCD) is a phenotypically and genetically heterogeneous disorder with an autosomal-recessive inheritance pattern. Only rarely other modes of inheritance such as X-linked transmission are observed. The disease phenotype is caused by defects of respiratory cilia, sperm tails and the cilia of the embryonic node. The lack of mucociliary clearance contributes to recurrent respiratory tract infections, that might progress to permanent lung damage (bronchiectasis). The goal of therapy is prevention of bronchiectasis. Male infertility due to sperm tail dysmotility is another frequent finding in PCD. Half of affected individuals have situs inversus (Kartagener's syndrome) due to randomization of left/right body asymmetry. Currently three genes (DNAI1, DNAH5, DNAH11) that encode for dynein proteins have been linked to recessive PCD. Mutations in RPGR located on the X chromosome have been identified in males with retinitis pigmentosa and PCD. As a screening test nasal nitric oxide (NO) measurement is widely used. Establishment of diagnosis currently relies on electron microscopy, direct evaluation of ciliary beat by light microscopy, and/or the novel method of high-resolution immunofluorecent analysis of respiratory cilia.

Ciliary Motility Disorders↗
PubMed2006

Axonemal localization of the dynein component DNAH5 is not altered in secondary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder characterized by recurrent airway infections and situs inversus in half of affected individuals. Diagnosis currently relies on demonstration of abnormal ciliary ultrastructure or altered ciliary beat. Alterations encountered in secondary ciliary dyskinesia (SCD) caused by inflammation often complicate the diagnostic workup. We have recently shown that in respiratory epithelial cells from PCD patients with outer dynein arm defects the dynein protein DNAH5 is mislocalized and either completely or partially absent from the ciliary axoneme. In this study, we addressed the question whether SCD might affect axonemal DNAH5 localization in respiratory cells. To induce SCD in vitro, we treated primary human respiratory epithelial cell cultures with interleukin-13 (IL-13). Ciliary function and ultrastructure were assessed by high-speed videomicroscopy and transmission electron microscopy, respectively. For in vivo localization of DNAH5, we performed nasal brushing biopsies in patients with evidence of SCD. Expression of DNAH5 was analyzed by immunofluorescence microscopy. IL-13-treated cells showed evidence of SCD. Ciliary beat frequency was significantly reduced and ultrastructural analyses showed axonemal disorganization compared with control cells. High-resolution immunofluorescence studies of respiratory epithelial cells with SCD identified in vitro and in vivo normal axonemal DNAH5 localization. DNAH5 localization is not altered by SCD, indicating a high potential for immunofluorescence analysis as a novel diagnostic tool in PCD.

Axonemal Dyneins↗
PubMed2001

Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and investigation of its role in primary ciliary dyskinesia.

Dyneins are multisubunit protein complexes that couple ATPase activity with conformational changes. They are involved in the cytoplasmatic movement of organelles (cytoplasmic dyneins) and the bending of cilia and flagella (axonemal dyneins). Here we present the first complete cDNA and genomic sequences of a human axonemal dynein beta heavy chain gene, DNAH9, which maps to 17p12. The 14-kb-long cDNA is divided into 69 exons spread over 390 kb. The cDNA sequence of DNAH9 was determined using a combination of methods including 5' rapid amplification of cDNA ends, RT-PCR, and cDNA library screening. RT-PCR using nasal epithelium and testis RNA revealed several alternatively spliced transcripts. The genomic structure was determined using three overlapping BACs sequenced by the Whitehead Institute/MIT Center for Genome Research. The predicted protein, of 4486 amino acids, is highly homologous to sea urchin axonemal beta heavy chain dyneins (67% identity). It consists of an N-terminal stem and a globular C-terminus containing the four P-loops that constitute the motor domain. Lack of proper ciliary and flagellar movement characterizes primary ciliary dyskinesia (PCD), a genetically heterogeneous autosomal recessive disorder with respiratory tract infections, bronchiectasis, male subfertility, and, in 50% of cases, situs inversus (Kartagener syndrome, KS). Dyneins are excellent candidate genes for PCD and KS because in over 50% of cases the ultrastructural defects of cilia are related to the dynein complex. Genotype analysis was performed in 31 PCD families with two or more affected siblings using a highly informative dinucleotide polymorphism located in intron 26 of DNAH9. Two families with concordant inheritance of DNAH9 alleles in affected individuals were observed. A mutation search was performed in these two "candidate families," but only polymorphic variants were found. In the absence of pathogenic mutations, the DNAH9 gene has been excluded as being responsible for autosomal recessive PCD in these families.

Adenosine Triphosphate↗
PubMed1992

HLA haplotype segregation and ultrastructural study in familial immotile-cilia syndrome.

The immotile-cilia syndrome (ICS) is a congenital disorder characterized by dysmotility or even complete immotility of the cilia in the ciliated epithelia. The most frequent consequences include recurrent airway infections from early childhood. Neonatal asphyxia often occurs. Males are usually sterile, whereas females may be fertile or infertile. The disease is inherited as an autosomal recessive trait, but previous attempts to localize the ICS susceptibility gene have so far been unsuccessful. Here, we present the case of two sib pairs affected by ICS from two unrelated families. The electron microscopic investigation of nasal biopsies showed structural anomalies of the cilia, characterized by single microtubules or doublets, arranged randomly in the axoneme. Histocompatibility antigen (HLA)-genotyping of all family members revealed: 1) a significant association of ICS with the HLA-DR7; DQW2 haplotype, which is shared by all the affected sibs (P = 0.0099; RR = 25.94); 2) a possible linkage of the ICS susceptibility gene with HLA, both the affected sibs being HLA-identical, the healthy brother in family B being HLA-different (sib-pair analysis: P less than 0.001).

Child, Preschool↗
PubMed1991

Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport?

Fucosidosis is caused by a deficiency of the lysosomal enzyme alpha-L-fucosidase (ALF) leading to an accumulation of glycoproteins in a variety of cells. Infants and young children with this disorder are prone to recurrent sinus and pulmonary infections and often die of pneumonia. We studied the mucociliary and systemic immune function in a 6 year old girl with fucosidosis and recurrent respiratory infections. All measurements of systemic immune function were normal. Sweat chloride was normal when measured on angiokeratotic skin but was greater than 65 mg/L on uninvolved areas. During the placement of tympanic ventilation tubes, tracheal mucus was gently aspirated and a mucosal biopsy was taken. Tracheal mucus transport was not measured. The biopsy material was examined under phase contrast microscopy and revealed ciliated cells with apparently normal beating. TEM of these cells showed a characteristic pattern of vacuoles in the cytoplasm as described in other tissues from patients with fucosidosis. Ciliary ultrastructure was normal. Mucus viscoelasticity was measured in a magnetic microrheometer. The loss tangent was 2 SD above the mean for normal mucus and mechanical impedance was about 2 SD below the mean. These changes are similar in direction but double in magnitude to what has been described with methacholine administration in dogs. The high compliance of the mucus may be due to incomplete assembly of mucus glycoprotein or to decreased secretion of glycoproteins in respiratory secretions. This leads to mucus that is abnormally watery and thus difficult to clear from the airway.

Child↗
PubMed1999

Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a group of heterogeneous disorders of unknown origin, usually inherited as an autosomal recessive trait. Its phenotype is characterized by axonemal abnormalities of respiratory cilia and sperm tails leading to bronchiectasis and sinusitis, which are sometimes associated with situs inversus (Kartagener syndrome) and male sterility. The main ciliary defect in PCD is an absence of dynein arms. We have isolated the first gene involved in PCD, using a candidate-gene approach developed on the basis of documented abnormalities of immotile strains of Chlamydomonas reinhardtii, which carry axonemal ultrastructural defects reminiscent of PCD. Taking advantage of the evolutionary conservation of genes encoding axonemal proteins, we have isolated a human sequence (DNAI1) related to IC78, a C. reinhardtii gene encoding a dynein intermediate chain in which mutations are associated with the absence of outer dynein arms. DNAI1 is highly expressed in trachea and testis and is composed of 20 exons located at 9p13-p21. Two loss-of-function mutations of DNAI1 have been identified in a patient with PCD characterized by immotile respiratory cilia lacking outer dynein arms. In addition, we excluded linkage between this gene and similar PCD phenotypes in five other affected families, providing a clear demonstration of locus heterogeneity. These data reveal the critical role of DNAI1 in the development of human axonemal structures and open up new means for identification of additional genes involved in related developmental defects.

Amino Acid Sequence↗
PubMed2006

Prevalence and genetics of immotile-cilia syndrome and left-handedness.

Immotile-cilia syndrome is characterized by severe respiratory distress from early infancy, and also often by situs inversus. The first description of the disease was based on just four persons, but reasons were given to suggest that the disorder may not be exceedingly rare. The purpose of the present study was to estimate just how rare or how common it is and to evaluate its association with situs inversus and with left-handedness. Data were mainly obtained from contacting a large number of Swedish clinicians who kindly informed us about their patients with suspected immotile-cilia syndrome. Diagnosis was in most cases performed by electron microscopical examination of nasal cilia or of spermatozoa. Based on these data, the prevalence of the syndrome in Sweden with or without situs inversus was estimated to be not far from 1 in 10,000. The syndrome consists of several subgroups that have a randomized determination of situs asymmetry (50% of these have situs inversus) and one subgroup in which situs inversus is not found. This results in a frequency of situs inversus in the syndrome of about 44 %. Left-handedness is no more common than it is in healthy persons and no more often associated with situs inversus than with situs solitus. In all cases it is about 14 %. It is concluded that the two major anatomical/physiological asymmetries of the human body are found with frequencies which indicate that they develop independently of each other. Both conditions appear with prevalences that may have changed at a centenary scale, left-handedness with a substantial increase and situs inversus with a less dramatic increase.

Adult↗
PubMed2000

Primary ciliary dyskinesia: a genome-wide linkage analysis reveals extensive locus heterogeneity.

Primary ciliary dyskinesia (PCD), or immotile cilia syndrome (ICS), is an autosomal recessive disorder affecting ciliary movement with an incidence of 1 in 20000-30000. Dysmotility to complete immotility of cilia results in a multisystem disease of variable severity with recurrent respiratory tract infections leading to bronchiectasis and male subfertility. Ultrastructural defects are present in ciliated mucosa and spermatozoa. Situs inversus (SI) is found in about half of the patients (Kartagener syndrome). We have collected samples from 61 European and North American families with PCD. A genome-wide linkage search was performed in 31 multiplex families (169 individuals including 70 affecteds) using 188 evenly spaced (19cM average interval) polymorphic markers. Both parametric (recessive model) and non-parametric (identity by descent allele sharing) linkage analyses were used. No major locus for the majority of the families was identified, although the sample was powerful enough to detect linkage if 40% of the families were linked to one locus. These results strongly suggest extensive locus heterogeneity. Potential genomic regions harbouring PCD loci were localised on chromosomes 3p, 4q, 5p, 7p, 8q, 10p, 11q, 13q, 15q, 16p, 17q and 19q. Linkage analysis using PCD families with a dynein arm deficiency provided 'suggestive' evidence for linkage to chromosomal regions 8q, 16pter, while analyses using only PCD families with situs inversus resulted in 'suggestive' scores for chromosomes 8q, and 19q.

Ciliary Motility Disorders↗
PubMed2005

Comparison of ciliary wave disorders measured by image analysis and electron microscopy.

CONCLUSION: We have developed a simple, reliable method for the simultaneous determination of the ciliary wave disorder (CWD) and ciliary beat frequency (CBF) of actively beating cilia. OBJECTIVE: The CBF and the directions of beating cilia are two important components of mucociliary transport. Although lots of studies have been performed on the measurement of the CBF, there have been few studies on the direction of cilia, with the exception of those using electron microscopy (EM). EM takes too long to determine the directions of cilia, and it cannot determine the direction of actively beating cilia. The aim of this study was to develop an image analysis (IA) system to conveniently determine the wave directions of multiple actively beating cilia as well as the CBF. MATERIAL AND METHODS: Sphenoid sinus mucosae obtained from 10 patients undergoing pituitary tumor removal via a trans-septal trans-sphenoidal approach were divided into two 4 x 4 mm2-sized pieces. One piece was studied using IA, the other with EM. Using IA, ciliary wave directions were determined from 5 20 x 20 microm2 regions of interest and the mean of 5 consecutive values was regarded as the CWD of each sample. The CBF was also measured. CWD was also measured using EM. RESULTS: The average number of cilia analyzed by EM was 102.50 (range 48-136). The mean CWDs determined using IA and EM were 28.25+/-4.84 degrees and 23.59+/-8.16 degrees, respectively. There was a significant correlation between the CWDs determined using these two methods (Spearman's correlation coefficient =0.648; p =0.043). The mean CBF of sphenoid mucosa was 10.50+/-2.20 Hz.

Adolescent↗
PubMed1992

Primary ciliary dyskinesia in the dog.

A disorder caused by congenital ciliary dysfunction occurs in dogs. Most of the clinical signs are directly or indirectly attributable to immotile or dyskinetic cilia and spermflagella. Due to severely impaired mucociliary clearance, a continuous mucoid nasal discharge and intermittent sneezing and coughing are typically observed during the neonatal period. Recurrent bacterial rhinosinusitis and bronchopneumonia usually start within a few weeks of birth. Hypoplastic nasal sinuses and atresia of the frontal sinuses are variable features of the disease that may be caused by neonatal colonization of these structures by specific bacteria. Bronchiectasis is an acquired lesion resulting from chronic inflammation and obstruction of airways. A secretory otitis media is caused by dysfunction of the cilia in the middle ear, and is manifested in some dogs by sclerotic tympanic bullae. Male infertility is caused by live, but immotile to hypomotile spermatozoa; however, unexplained oligospermia and azoospermia have been reported. Hydrocephalus and situs inversus are common but variable features of the disease; the genesis of these lesions has not yet been determined. The probable mode of inheritance is autosomal recessive, but dominant mutations cannot be excluded. The diagnosis can be confirmed by demonstrating the absence or near absence of nasal or tracheal mucociliary clearance and the presence of a specific ultrastructural lesion in a large percentage of cilia from multiple sites (airways, middle ear, or oviduct). The ultrastructure of sperm flagella should mirror that of the cilia. Not all dogs have ultrastructural ciliary lesions, and in these cases, results of in vitro analysis of ciliary activity may be highly suggestive, if not diagnostic. In dogs without mucociliary clearance in which structural and functional analysis of cilia are not diagnostic, confirmation of congenital ciliary dysfunction can be established only by ruling out other diseases with similar signs (e.g., congenital immunodeficiency syndromes). The clinical course in an longevity of affected dogs are highly variable. Appropriate antibiotic treatment and pulmonary physical therapy may result in prolonged survival, although cor pulmonale and reactive systemic amyloidosis are potential sequelae of chronic hypoxia and chronic bacterial infection of the airways, respectively.

Animals↗