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Centrioles and cilia in non-tumourous anterior lobes and adenomas of the human pituitary.

Electron microscopy revealed the presence of centrioles and cilia in non-tumourous adenohypophysiocytes as well as in various adenomas of the human pituitary gland. Accumulation of centrioles and cilia was evident in sparsely granulated growth hormone cell adenomas. Abundance of centrioles is a valuable sign in establishing the diagnosis of this tumour. The possible functional significance of centrioles and cilia in adenohypophysial cells has been discussed.

Adenoma↗

Genetic aspects of immotile cilia syndrome.

The genetics of the immotile cilia syndrome has been analyzed in a series of 46 affected individuals from 38 families. Both sexes were equally affected: there were 20 males and 26 females in this series. All patients had upper and lower respiratory disease with chronic sinusitis, otitis, and chronic cough from early childhood. Bronchiectasis was common in older children and adults. Situs inversus occurred randomly, affecting 11 males and 15 females. Biopsies of nasal and bronchial mucosa from these subjects have been investigated by electron microscopy and identified as having specific ultrastructural defects of respiratory tract cilia including deficiencies in outer dynein arms (19), inner dynein arms (3), both inner and outer dynein arms (15), radial spoke defect (5); and microtubular transposition anomaly (4). Segregation analysis of proband sibships was consistent with autosomal recessive inheritance. However, the different ultrastructural defects that underly the immotile cilia syndrome involve presumably different genetic determinants, and the different types have not been analyzed separately. Examination of paternal age and birth order gave no evidence of new autosomal dominant mutation in the series.

Ciliary Motility Disorders↗

Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers-Manes Kartagener and Bjorn Afzelius.

The relationship of Kartagener's syndrome to immobile cilia syndrome is a fascinating merging of clinical observations and basic science in Zurich, Stockholm, and Toronto. In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus. In the following decades, he reviewed reports of hundreds of cases, but the fact that the male patients with the condition never had offspring eluded his notice. In the 1970s, Bjorn Afzelius, a Ph.D. ultrastructuralist from Stockholm, reported cilia immotility in infertile males, some of the cases occurring in families. Half of the cases had Kartagener's triad. The observation of Afzelius was soon applied to children by Jennifer Sturgess, a Ph.D. ultrastructuralist, and her medical colleagues in Toronto. With over 500 MEDLINE references since 1966 on Kartagener's and over 1,000 references on immotile cilia, the causes of the pulmonary infections have become clearer as the patients demonstrate impaired clearance of mucus with resultant sinus and bronchial disease. The cause of the situs inversus remains elusive to this day. It is appropriate to call the condition Kartagener-Afzelius syndrome.

Canada↗

The Tetrahymena chaperonin subunit CCT eta gene is coexpressed with CCT gamma gene during cilia biogenesis and cell sexual reproduction.

We report here the cloning and the characterization of the T. pyriformis CCT eta gene (TpCCT eta) and also a partial sequence of the corresponding T. thermophila gene (TtCCT eta). The TpCCt eta gene encodes a protein sharing a 60.3% identity with the mouse CCT eta. We have studied the expression of these genes in Tetrahymena exponentially growing cells, cells regenerating their cilia for different periods and during different stages of the cell sexual reproduction. These genes have similar patterns of expression to those of the previously identified TpCCt gamma gene. Indeed, the Tetrahymena CCT eta and CCT gamma genes are up-regulated at 60-120 min of cilia recovery, and in conjugation when vegetative growth was resumed and cell division took place. Our results seem to indicate that both CCT subunits play an important role in the biogenesis of the newly synthesized cilia of Tetrahymena and during its cell division.

Amino Acid Sequence↗

The immotile cilia syndrome--one cause of persistent upper respiratory tract infection.

Four patients with persistent recurrent upper respiratory tract infections are presented. Electron microscopic studies of respiratory mucosal biopsies from these patients reveal ultrastructural abnormalities of cilia consisting of partial to complete loss of dynein arms, radial spoke disruption, and compound cilia. The concept of immotile cilia as an important cause of recurrent infections is receiving more attention. This study stresses the need for simple, rapid screening tests for cilial activity followed by electron microscopic evaluation in selected cases.

Biopsy↗

Birth after intracytoplasmic sperm injection with use of testicular sperm from men with Kartagener/immotile cilia syndrome.

OBJECTIVE: To describe two cases of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with testicular sperm in men with immotile cilia syndromes. DESIGN: Case report. SETTING: A university-based male infertility clinic and assisted reproduction unit. PATIENT(S): Two couples with male factor infertility due to Kartagener/immotile cilia syndrome. INTERVENTION(S): IVF/ICSI with testicular sperm. MAIN OUTCOME MEASURE(S): Semen characteristics, sperm viability, fertilization rate, and pregnancy. RESULT(S): With testicular sperm, the two pronuclear fertilization rates were 63% and 60% in two cases. One case resulted in the birth of normal healthy girl. CONCLUSION(S): With testicular sperm, successful oocyte fertilization after ICSI in couples with male Kartagener/immotile cilia syndrome is possible despite the lack of sperm motility.

Adult↗

Left-right development: the roles of nodal cilia.

Cilia on the ventral side of the mouse node have been implicated in initiating the left-right axis during embryonic development, but how cilia relate to other factors in the left-right pathway and the mechanism by which cilia convey patterning information remain uncertain.

Animals↗

Pregnancy after ICSI with ejaculated immotile spermatozoa from a patient with immotile cilia syndrome: a case report and review of the literature.

This study presents a case of intracytoplasmic sperm injection (ICSI) with ejaculated immotile spermatozoa from a patient with immotile cilia syndrome. Semen analysis of the patient suffering from immotile cilia syndrome revealed an extreme oligoasthenoteratozoospermia (OAT: count <1.4 x 10(6)/ml, 0% motility and 3% normal morphology). Electron microscopy of sperm flagella showed the absence of inner and outer dynein arms. During the ICSI cycle, the hypo-osmotic swelling test (HOS) was used for the identification of viable spermatozoa in the pool of immotile spermatozoa for ICSI. A normal fertilization rate was found in eight out of the 12 oocytes. A first fresh double embryo transfer resulted in a late miscarriage at 21 weeks. A second healthy singleton pregnancy occurred after transfer of two frozen-thawed embryos from the same ICSI procedure. Although only one successful ICSI case of the immotile cilia syndrome combined with HOS is described here, HOS might be a simple but valuable tool to obtain normal fertilization and pregnancy for patients suffering from immotile spermatozoa.

Adult↗

R1 region of P97 mediates adherence of Mycoplasma hyopneumoniae to swine cilia.

Adherence of Mycoplasma hyopneumoniae to the swine respiratory tract is mediated by the membrane protein P97. This protein is located on the outer membrane surface, and its role in adherence has been firmly established. The general region of P97 that mediates adherence to swine cilia is thought to be the R1 region near the carboxy terminus of the protein, but it was not clear if this region could mediate adherence to swine cilia independently of other P97 sequences. To examine this in more detail, a series of R1 repeat sequences containing different numbers of repeating units cloned in frame with lacZ was used to produce R1-beta-galactosidase fusion proteins. These proteins were then tested for adherence to swine cilia and for reactivity to the adherence-blocking monoclonal antibody F2G5 and convalescent-phase swine sera. In this way it was possible to accurately define the cilium binding epitope of P97 and the minimal epitope recognized by antibody. Our results indicate that eight R1 repeating units are required for cilium binding and that three repeating units are needed for antibody recognition. These results could lead to more effective therapeutic measures against this important swine pathogen.

Adhesins, Bacterial↗

Bronchitis and bronchiolitis in a cat with cilia-associated respiratory bacillus-like organisms.

A 10-year-old male domestic shorthair cat died during anesthesia. Grossly, the lungs had multiple nodules corresponding to inflamed airways (bronchitis and bronchiolitis). Microscopically, cuffs and nodular aggregates of lymphocytes and plasma cells surrounded airways. Peribronchiolar fibrosis was also common. Globule leukocytes infiltrated the respiratory epithelium of noninflamed or mildly inflamed bronchi. Argyrophilic and filamentous organisms, consistent with cilia-associated respiratory bacillus-like organisms (CLO), were intermixed with cilia of respiratory epithelium. Ultrastructurally, CLO were longer and thinner than cilia and had a distinct trilaminar membrane, central electron-lucent areas, and no specialized external structures. Silver stained lung sections from 18 additional feline airways revealed similar bacilli in 2/9 normal lungs, 1/7 lungs with bronchitis and bronchiolitis, and 1/2 lungs with pneumonia. The significance of CLO in the pulmonary lesions was not determined.

Animals↗

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↗

[A case of immotile-dyskinetic cilia syndrome responding to clenbuterol hydrochloride and azithromycin].

In this case, a 30-year-old man had been treated for chronic sinusitis and bronchiectasis since 2000, and presented at our outpatient clinic in May 2001 with chief complaints of massive yellow sputum expectoration and dyspnea. After he was admitted by our hospital, Pseudomonas aeruginosa bacteria were isolated at the rate of 10(8)/ml from his sputum culture. In electron-microscopic observation, the cilia of the bronchial epithelium were found to lack dynein arms. Semen examination revealed decreased sperm motility. Thus, the following diagnosis was made: diffuse bronchiectasis associated with the immotile-dyskinetic cilia syndrome, complicated with a P. aeruginosa infection. After the airway infection was ameliorated, 40 mg/day of clenbuterol hydrochloride was administered in combination with 250 mg of azithromycin, which was given twice a week, and which led to a markedly decreased frequency of exacerbation of airway infection. Moreover, chest CT scanning and respiratory function testing also indicated improvements. It was hypothesized that the decreased cilia motility due to P. aeruginosa-produced pyocyanin would be ameliorated with a b2 stimulant, and the inhibitory effect of a macrolide on the P. aeruginosa biofilm and production of pyocyanin would also be involved in the improvement of this case.

Adult↗

[Intraocular cilia with macular pucker: clinicopathologic correlation].

PURPOSE/METHODS: To report the pathological findings in a case of intravitreous cilia with macular pucker. We considered clinical factors to establish treatment. A pars plana vitrectomy and premacular membrane peeling were performed. Surgical samples were removed and studied with PAS, hematoxylin-eosin, Masson's Trichromic and immunohistochemistry. RESULTS/CONCLUSION: The histopathological examination disclosed the presence of cilia partially surrounded by a cuticle layer and internal limiting membrane with a celullarity increase. Surgical extraction is indicated in those cases in which the intraocular cilia are associated with any surgically treatable process or when it produces ocular inflammation or visual disturbance.

Adult↗

Recurrent respiratory disease, azoospermia, and nasal polyposis. A syndrome that mimics cystic fibrosis and immotile cilia syndrome.

Three adult men with chronic sinopulmonary disease, nasal polyposis, and azoospermia were studied. All had normal sweat chloride values and pancreatic function. The azoospermia was due to a block in the epididymis that was distinguishable from the defect in the vas deferens seen in cystic fibrosis. Cilia structure was normal in sperm tails from testicular biopsy specimens and in cilia from tracheal biopsy specimens. These cases represent a clinical entity distinct from cystic fibrosis and known immotile cilia disorders.

Adult↗

Immotile cilia syndrome in pigs. A model for human disease.

This paper describes the ultrastructural alterations observed in the tracheal epithelium of six sibling swine suffering from porcine immotile cilia syndrome (PICS) compared with those in human immotile cilia syndrome (HICS). As in some human cases, the tracheal epithelium of these pigs was lined by cilia-lacking cells. A variety of dynein defects in other pigs suffering from PICS have been previously observed. The spectrum of defects affords evidence that the PICS is genetically heterogeneous. Available data suggests that there are many similarities between HICS and PICS. Therefore, it is proposed that PICS may prove to be a useful animal model for the human disease.

Animals↗

Cilia regrowth of shaven eyebrows.

OBJECTIVE: To determine if shaving eyebrows can lead to permanent brow loss. METHODS: Five patients had a single brow randomly shaven, while the unshaven brow served as a control. These patients were evaluated prospectively for brow regrowth during 6 months, and photographs were taken at each visit. Two masked observers analyzed the final photographs to determine if they could identify the side that was shaven. RESULTS: All patients had full brow regrowth by 6 months. The masked observers could not identify shaven side with any consistency. One female patient with sparser, lighter-colored brow cilia waited longer than the other patients for full brow regrowth. CONCLUSION: This small study demonstrates for the first time that full brow cilia regrowth is possible after completely shaving an eyebrow.

Adult↗

Cilia-driven rotational behavior in gastropod (Physa elliptica) embryos induced by serotonin and putative serotonin reuptake inhibitors (SSRIs).

We characterized the serotonin (5-hydroxytryptamine; 5-HT) receptor mediating cilia-driven rotational movement in embryos of the freshwater gastropod Physa elliptica. In addition, putative serotonin reuptake inhibitors (SSRIs), previously shown to induce other 5-HT-mediated processes in molluscs, were tested for their ability to induce rotation. As in previous studies with other freshwater gastropods, 5-HT induced a significant dose-dependent increase in rotation from 10(-6) to 10(-4) M. The 5-HT(1A) agonist 8-OH-DPAT produced a similar dose-dependent increase in rotation. However, the 5-HT(2) agonist alpha-CH3-serotonin evoked a significant rotational response only at the highest concentration of 10(-4) M. The 5-HT(2) receptor antagonist mianserin not only blocked 5-HT-induced rotation, it reduced rotation rate below that of baseline. However, two other antagonists, cyproheptadine (5-HT(2)) and propranolol (5-HT(1)), caused similar responses that consisted of an initial rotational surge followed by reduced rotation. Thus, these drugs appear to act as partial agonists. The putative SSRI fluvoxamine exhibited a significant dose-dependent increase in positive rotation as that seen with 5-HT. The SSRIs paroxetine and fluoxetine both caused an increase in rotation at 10(-6) and 10(-5) M but reduced rotation rate below that of baseline at 10(-4) M. These results agree with other studies on aquatic molluscs, suggest a 5-HT receptor with a mixed 5-HT(1)/5-HT(2) pharmacological profile and add to a now growing body of literature on the pharmacology of molluscan 5-HT receptors. In addition, all the tested putative SSRIs induced cilia-driven rotation in Physa embryos, indicating either the presence of 5-HT reuptake transporters or that these compounds act as 5-HT receptor ligands. J. Exp. Zool. 286:414-421, 2000.

Animals↗

Ultrastructural studies of the female breast: I. 9 + 0 cilia in myoepithelial cells.

9 + 0 cilia associated with diplosomes were observed in myoepithelial cells of the ductal system in the undiseased, resting, adult female breast. Ciliary diameter was 250 nm, and the longest found was 830 nm. The centrioles comprising the diplosome were 500 nm in length and 160 to 200 nm in diameter. Satellite bodies were associated with the diplosome but there was no rootlet system. Evidence suggested that all myoepithelial cells bear a cilium. The possible functions of the cilia in a sensory role as chemo- or mechanoreceptors related to myoepithelial and epithelial activities are discussed.

Adult↗