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1.
Ultrasound Q ; 40(3)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38991142

ABSTRACT

ABSTRACT: Cranial ultrasound (CUS) is an indispensable tool in the evaluation of intracranial pathology in premature and term neonates and older infants. Familiarity with standard cranial ultrasound techniques and parameters, normal anatomy, and commonly encountered abnormalities is crucial for providing appropriate care for these patients. This review provides a comprehensive overview of cranial ultrasound in clinical practice.


Subject(s)
Echoencephalography , Humans , Infant, Newborn , Infant , Echoencephalography/methods , Brain/diagnostic imaging , Child , Brain Diseases/diagnostic imaging , Ultrasonography/methods , Child, Preschool
3.
Curr Probl Diagn Radiol ; 52(6): 485-492, 2023.
Article in English | MEDLINE | ID: mdl-37248135

ABSTRACT

Lengthy MRI examinations in young children often requires sedation. When sedation is unavailable, critical imaging may be delayed. Abbreviating the imaging protocol to a few essential sequences may reduce the need for sedation and prevent delays in patient care. We retrospectively evaluated an abbreviated noncontrast MRI protocol to diagnose lower extremity osteomyelitis in the pediatric population. The IRB approved this study. The radiology information system was searched for lower extremity MRI examinations for osteomyelitis in patients <20 years old from August 2020 to August 2021. Three noncontrast sequences (long axis T1 without fat saturation (FS), long axis STIR, and axial T2 with FS) were independently reviewed by 2 pediatric radiologists. The accuracy of the reviewers was compared to the clinical radiology report based on the unabridged contrast-enhanced standard department protocol. The search yielded 80 exams, mean age was 7 years old, 59% (47/80) were male, and 41% (33/80) were female. The accuracies of reviewer A and reviewer B were 95% and 89%, respectively. The reviewer inter-observer agreement for the diagnosis of osteomyelitis was strong (k = 0.79). The accuracy of an abbreviated noncontrast MRI protocol to evaluate lower extremity osteomyelitis in children approaches that of the unabridged protocol and has the potential to decrease the need for sedation in young children.

5.
Radiographics ; 42(5): 1514-1531, 2022.
Article in English | MEDLINE | ID: mdl-35839138

ABSTRACT

When a pediatric hepatic cystic lesion is identified at imaging, the differential diagnosis may be broad, including developmental, infectious, neoplastic, and posttraumatic or iatrogenic causes. The location of a cystic lesion and its number, size, composition, and relationship to the biliary system are features that help in narrowing the differential diagnosis. An incidentally detected simple hepatic cyst is the most commonly encountered. Ciliated foregut cysts are typically located in hepatic segment IVa. The presence of multiple cysts should raise suspicion for fibropolycystic liver disease, a group of related lesions-including biliary hamartoma and choledochal cyst-caused by abnormal embryologic development of the ductal plate. Communication of the cystic lesion with the biliary tree can confirm the diagnosis of choledochal cyst. In a neonate with jaundice, a cystic lesion at the porta hepatis should raise suspicion for choledochal cyst versus cystic biliary atresia. Hepatic abscess can appear cystlike, though typically with internal contents. In an immunocompromised child, multiple cystlike lesions should raise concern for fungal microabscesses. A complex cystic mass in a young child should raise suspicion for mesenchymal hamartoma, which can evolve into undifferentiated embryonal sarcoma if untreated. Hepatic hematoma and biloma can appear cystlike in children with a history of trauma or recent intervention. In neonates with an umbilical vein catheter (UVC), an intrahepatic cyst along the course of the UVC should raise concern for infusate extravasation. Familiarity with imaging findings and clinical features is essential for achieving accurate diagnosis of pediatric hepatic cystic lesions, which in turn can guide appropriate clinical management. Online supplemental material is available for this article. ©RSNA, 2022.


Subject(s)
Choledochal Cyst , Hamartoma , Liver Neoplasms , Child , Choledochal Cyst/diagnosis , Cysts , Diagnosis, Differential , Hamartoma/diagnostic imaging , Humans , Infant, Newborn , Liver Diseases , Liver Neoplasms/diagnostic imaging , Multimodal Imaging
6.
Pediatr Radiol ; 52(3): 477-482, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34850259

ABSTRACT

BACKGROUND: Early and accurate radiographic diagnosis is required for the management of children with radio-opaque esophageal foreign bodies. Button batteries are some of the most dangerous esophageal foreign bodies and coins are among the most common. We hypothesized that artificial intelligence could be used to triage radiographs with esophageal button batteries and coins. OBJECTIVE: Our primary objective was to train an object detector to detect esophageal foreign bodies, whether button battery or coin. Our secondary objective was to train an image classifier to classify the detected foreign body as either a button battery or a coin. MATERIALS AND METHODS: We trained an object detector to detect button batteries and coins. The training data set for the object detector was 57 radiographs, consisting of 3 groups of 19 images each with either an esophageal button battery, esophageal coin or no foreign body. The foreign bodies were endoscopically confirmed, and the groups were age and gender matched. We then trained an image classifier to classify the detected foreign body as either a button battery or a coin. The training data set for the image classifier consisted of 19 radiographs of button batteries and 19 of coins, cropped from the object detector training data set. The object detector and image classifier were then tested on 103 radiographs with an esophageal foreign body, and 103 radiographs without a foreign body. RESULTS: The object detector was 100% sensitive and specific for detecting an esophageal foreign body. The image classifier accurately classified all 6/6 (100%) button batteries in the testing data set and 93/95 (97.9%) of the coins. The remaining two coins were incorrectly classified as button batteries. In addition to these images with a single button battery or coin, there were two unique cases in the testing data set: a stacked button battery and coin, and two stacked coins, both of which were classified as coins. CONCLUSION: Artificial intelligence models show promise in detecting and classifying esophageal discoid foreign bodies and could potentially be used to triage radiographs for radiologist interpretation.


Subject(s)
Artificial Intelligence , Foreign Bodies , Child , Electric Power Supplies , Esophagus/diagnostic imaging , Foreign Bodies/diagnostic imaging , Humans , Infant , Numismatics
8.
Pediatr Radiol ; 51(2): 231-238, 2021 02.
Article in English | MEDLINE | ID: mdl-33404786

ABSTRACT

BACKGROUND: Although the radiographic features of coronavirus disease 2019 (COVID-19) in children have been described, the distinguishing features of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 are not well characterized. OBJECTIVE: We compared the chest radiographic findings of MIS-C with those of COVID-19 and described other distinguishing imaging features of MIS-C. MATERIALS AND METHODS: We performed a retrospective case series review of children ages 0 to 18 years who were hospitalized at Children's Healthcare of Atlanta from March to May 2020 and who either met the Centers for Disease Control and Prevention (CDC) case definition for MIS-C (n=11) or who had symptomatic, laboratory-confirmed COVID-19 (n=16). Two radiologists reviewed the most severe chest radiographs for each patient. The type and distribution of pulmonary opacities and presence or absence of pleural effusions were recorded. The chest radiographs were categorized based on potential COVID-19 imaging findings as typical, indeterminate, atypical or negative. An imaging severity score was also assigned using a simplified version of the Radiographic Assessment of Lung Edema Score. Findings were statistically compared between patients with MIS-C and those with COVID-19. Additional imaging findings of MIS-C were also described. RESULTS: Radiographic features of MIS-C included pleural effusions (82% [9/11]), pulmonary consolidations (73% [8/11]) and ground glass opacities (91% [10/11]). All of the lung opacities (100% [10/10]) were bilateral, and the majority of the pleural effusions (67% [6/9]) were bilateral. Compared to children with COVID-19, children with MIS-C were significantly more likely to develop pleural effusions on chest radiograph (82% [9/11] vs. 0% [0/0], P-value <0.01) and a lower zone predominance of pulmonary opacifications (100% [10/10] vs. 38% [5/13], P-value <0.01). Children with MIS-C who also had abdominal imaging had intra-abdominal inflammatory changes. CONCLUSION: Key chest radiographic features of MIS-C versus those of COVID-19 were pleural effusions and lower zone pulmonary opacifications as well as intra-abdominal inflammation. Elucidating the distinguishing radiographic features of MIS-C may help refine the case definition and expedite diagnosis and treatment.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/pathology , Lung/diagnostic imaging , Lung/pathology , Radiography, Thoracic/methods , Systemic Inflammatory Response Syndrome/diagnostic imaging , Systemic Inflammatory Response Syndrome/pathology , Adolescent , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Infant , Male , Retrospective Studies , SARS-CoV-2
9.
AJR Am J Roentgenol ; 215(5): 1238-1246, 2020 11.
Article in English | MEDLINE | ID: mdl-32960667

ABSTRACT

OBJECTIVE. The purpose of this study was to evaluate findings at serial MRI after endoscopic removal of a button battery from the esophagus in a series of pediatric patients. MATERIALS AND METHODS. Serial MRI examinations after removal of a button battery from the esophagus were reviewed retrospectively for the presence of mediastinal edema; imaging characteristics of the aorta and arteries; imaging characteristics of the trachea; and imaging characteristics of the esophageal wall at the level of injury. RESULTS. A total of 48 MRI examinations were performed on 19 patients, 89% (17/19) in the first 48 hours after battery removal. Serial MRI was performed for 84% (16/19) of patients. Initial MRI showed extensive mediastinal edema in all 17 patients who underwent MRI in the first 48 hours. Edema directly abutted major arteries in all 17 patients and abutted the airway in all 10 patients with proximal esophageal injury. Arterial vascular changes were seen in 30% (3/10) of patients with proximal esophageal injury and 57% (4/7) of patients with mid or distalesophageal injury. Airway changes were seen in 80% (8/10) of patients with proximal esophageal injury. Serial MRI showed improvement of airway changes in all patients and improvement in vessel wall changes in all but one (25%, 1/4) of the patients who had mid or distal esophageal injury. Four patients (21% [4/19]) had contained esophageal leak on esophagrams. No patients in our series developed a tracheoesophageal or vascular-enteric fistula. CONCLUSION. Our case series provides important information on natural history of MRI findings in children after endoscopic removal of a button battery from the esophagus. Further studies are needed to determine the imaging findings most sensitive and specific for severe complications, such as tracheoesophageal fistula and vascular-enteric fistula.


Subject(s)
Esophagoscopy , Esophagus/diagnostic imaging , Esophagus/injuries , Foreign Bodies/complications , Foreign Bodies/surgery , Magnetic Resonance Imaging/methods , Child , Child, Preschool , Electric Power Supplies , Female , Humans , Infant , Male , Postoperative Period , Retrospective Studies
10.
Pediatr Radiol ; 50(9): 1249-1254, 2020 08.
Article in English | MEDLINE | ID: mdl-32519054

ABSTRACT

BACKGROUND: Ileocolic intussusception is a common cause of intestinal obstruction in young children. Radiographs may be of limited value in the diagnosis of intussusception and are sometimes utilized primarily to exclude pneumoperitoneum before therapeutic enema reduction. OBJECTIVE: The goal of this study was to determine if radiographic findings in ileocolic intussusception can offer prognostic information regarding the outcome of therapeutic air enema and, for those requiring surgical intervention, surgical outcomes and/or complications. MATERIALS AND METHODS: A single institution retrospective study was performed including all enemas for intussusception performed during a 5-year period from September 2012 to August 2017. Radiographs obtained before therapeutic enema, including our institution radiographs, outside facility radiographs, or scout images obtained during fluoroscopy or computed tomography (CT), were independently scored by two pediatric radiologists for normal bowel gas pattern, soft-tissue mass, paucity of bowel gas, meniscus sign and bowel obstruction. The reviewers were blinded to enema and surgical outcomes at the time of review. Differences were resolved by consensus. Cases were excluded in which there was no adequate pre-procedure radiograph. In total, 182 cases were reviewed. The medical records were reviewed for enema and surgical outcomes. RESULTS: Radiographic findings included normal bowel gas pattern in 13%, soft-tissue mass in 26%, paucity of bowel gas in 65%, meniscus sign in 12% and obstruction in 10% of the cases, with 17.5% of patients having more than one finding. In patients with bowel obstruction on radiographs, there was a statistically significant decrease in success of therapeutic enema (83% vs. 21%, P=0.0001), increase in complicated surgical reductions (47% vs. 4%, P=0.0012), and increase in bowel resection (42% vs. 4%, P=0.003) compared to patients with normal bowel gas pattern. CONCLUSION: Radiographs can offer prognostic information regarding the potential for therapeutic enema success, as well as potential surgical outcomes in patients failing enema reduction. Particularly, bowel obstruction significantly decreases the success of therapeutic enema and increases the need for bowel resection.


Subject(s)
Ileal Diseases/diagnostic imaging , Ileal Diseases/therapy , Intussusception/diagnostic imaging , Intussusception/therapy , Air , Child, Preschool , Enema , Female , Fluoroscopy , Humans , Infant , Male , Predictive Value of Tests , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
11.
Pediatr Radiol ; 50(8): 1102-1106, 2020 07.
Article in English | MEDLINE | ID: mdl-32462306

ABSTRACT

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is a common cause of gastric outlet obstruction in young infants. Infants with HPS present with projectile vomiting, sometimes have electrolyte abnormalities and typically undergo pyloromyotomy to alleviate the obstruction. Abdominal US is the gold standard imaging study for diagnosis. Case reports of incidental hepatic portal venous gas have been reported in infants with HPS; however, no large studies have been conducted to determine the incidence or possible clinical implications of this finding. OBJECTIVE: To assess the incidence of portal venous gas in infants with HPS and to determine whether the presence of this gas in infants with HPS indicates a more unstable patient, increased length of stay or worse outcome. MATERIALS AND METHODS: We conducted a retrospective review of sonographic reports containing "pyloric stenosis," excluding negative descriptor, at a tertiary-care children's hospital from November 2010 to September 2017. Data collected included pyloric thickness/length, liver evaluation, portal venous gas, any additional imaging, demographics, symptomatology days, electrolyte abnormality, and length of hospital stay. RESULTS: In a 7-year period, 545 US exams were positive for HPS. Of these, 334 exams included enough hepatic parenchyma to evaluate for portal venous gas. Infants in 6 of the 334 exams demonstrated portal venous gas (1.8%). Clinical presentation (length of symptoms and electrolyte abnormalities), demographics (male predominance and age at presentation) and imaging characteristics (pyloric thickness and length) were similar for the HPS groups with and without portal venous gas. There was no significant difference in outcome or length of hospital stay. CONCLUSION: Visualization of portal venous gas in infants with HPS is not rare and appears benign, without need for further imaging. Portal venous gas in infants with HPS does not portend a more severe patient presentation or outcome.


Subject(s)
Portal Vein/diagnostic imaging , Pyloric Stenosis, Hypertrophic/diagnostic imaging , Ultrasonography/methods , Female , Gases , Hospitals, Pediatric , Humans , Incidence , Incidental Findings , Infant , Infant, Newborn , Male , Retrospective Studies
12.
Emerg Radiol ; 27(1): 97-102, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31617106

ABSTRACT

Colocolic intussusception is a variation of intussusception that is rarely encountered in pediatric patients and as such can prove to be a diagnostic challenge for both the emergency clinician and radiologist. Knowledge of the presentation and imaging findings in these cases can expedite diagnosis and guide the patient to appropriate treatment. The demographics, clinical symptoms, imaging findings, and eventual surgical and pathologic outcomes of 8 children with colocolic intussusception will be presented in this pictorial essay, with a review of the available literature.


Subject(s)
Colonic Diseases/diagnostic imaging , Intussusception/diagnostic imaging , Adolescent , Child , Child, Preschool , Colonic Diseases/therapy , Diagnosis, Differential , Female , Humans , Infant , Intussusception/therapy , Male
13.
J Pediatr Surg ; 51(11): 1778-1781, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27320840

ABSTRACT

BACKGROUND/PURPOSE: Spontaneous pneumomediastinum is an infrequent condition in pediatric patients. Presenting symptoms include chest pain, dysphagia, or vomiting, without initiating event. Patients may undergo esophagram because of concern for esophageal perforation as the source for pneumomediastinum, however, abnormalities are rarely demonstrated. The objective of this study is to identify whether esophagrams performed on pediatric patients for spontaneous pneumomediastinum are warranted. METHODS: An IRB approved, retrospective study was performed. The radiology information system was queried for the keyword "pneumomediastinum" in reports from 2000 to 2016. 27 patients were identified with spontaneous pneumomediastinum, who underwent 28 esophagrams, and 18 patients with pneumomediastinum secondary to blunt trauma, undergoing 20 esophagrams. Imaging findings recorded included presence of pneumothorax or pleural effusion, amount of imaging performed, radiation dose and fluoroscopy time for esophagrams, and type of contrast used. Clinical data recorded included presenting symptoms, presence of fever, and length of hospital stay. RESULTS: All esophagrams in patients with both spontaneous and post traumatic pneumomediastinum were negative. Patients were exposed to radiation doses between 61 and 92 µGy m2 during esophagrams. Contrast aspiration occurred in one patient. CONCLUSIONS: Esophagrams are not indicated for pediatric patients with spontaneous pneumomediastinum, and may not be warranted in patients with post traumatic pneumomediastinum.


Subject(s)
Esophageal Perforation/complications , Esophageal Perforation/diagnostic imaging , Mediastinal Emphysema/diagnostic imaging , Mediastinal Emphysema/etiology , Adolescent , Child , Child, Preschool , Female , Fluoroscopy , Humans , Male , Radiation Exposure/statistics & numerical data , Radiography , Retrospective Studies , Tomography, X-Ray Computed
14.
Clin Imaging ; 40(2): 247-50, 2016.
Article in English | MEDLINE | ID: mdl-26995581

ABSTRACT

Tarsal coalition is relatively frequent, with an estimated prevalence of 1-2%. Coalitions are most commonly talocalcaneal or calcaneonavicular, accounting for 90% of cases. While it is well known that bilateral tarsal coalitions can occur in up to 50% of cases, the presence of multiple coalitions in the same foot is less well described. In this report, we present a case of talocalcaneal and calcaneonavicular coalitions occurring in the same foot and briefly review the relevant literature.


Subject(s)
Synostosis/diagnostic imaging , Tarsal Bones/diagnostic imaging , Adolescent , Humans , Male
15.
Case Rep Genet ; 2014: 273423, 2014.
Article in English | MEDLINE | ID: mdl-25215250

ABSTRACT

A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child's pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency.

16.
J Cell Sci ; 125(Pt 20): 4761-9, 2012 Oct 15.
Article in English | MEDLINE | ID: mdl-22797917

ABSTRACT

The innate immune system is a vital part of the body's defences against viral pathogens. The proteins retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) function as cytoplasmic pattern recognition receptors that are involved in the elimination of actively replicating RNA viruses. Their location and their differential responses to RNA viruses emphasises the complexity of the innate detection system. Despite the wealth of information on the types of RNA that trigger RIG-I, much less is known about the nature of the RNAs that act as agonists for MDA5. In order to identify which RNA species triggers MDA5 activation during infection, we isolated viral ssRNA and replicative intermediates of RNA from positive sense ssRNA viruses. We reveal that MDA5 recognises not the genomic ssRNA but the dsRNA generated by the replication of these viruses. Furthermore, using fluorescent imaging we present the first report of the visualisation of dsRNA and MDA5, which provides unique evidence of the relationship between viral dsRNA and MDA5 and proves without a doubt that MDA5 is the key sensor for the dsRNA replicative intermediate form of positive sense ssRNA viruses.


Subject(s)
DEAD-box RNA Helicases , RNA Viruses , RNA, Double-Stranded , Adult , DEAD Box Protein 58 , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/immunology , DEAD-box RNA Helicases/metabolism , Enterovirus/genetics , Enterovirus/metabolism , Female , HEK293 Cells , Humans , Immunity, Innate/genetics , Infections/genetics , Infections/immunology , Interferon-Induced Helicase, IFIH1 , Melanoma/genetics , Melanoma/immunology , Muscle Cells/cytology , Muscle Cells/metabolism , RNA Viruses/genetics , RNA Viruses/immunology , RNA Viruses/metabolism , RNA, Double-Stranded/genetics , RNA, Double-Stranded/immunology , RNA, Double-Stranded/metabolism , Receptors, Immunologic , Signal Transduction/genetics , Signal Transduction/immunology , Virus Replication/genetics
17.
J Cardiovasc Comput Tomogr ; 6(4): 260-7, 2012.
Article in English | MEDLINE | ID: mdl-22732199

ABSTRACT

BACKGROUND: Accurate coronary artery calcium scoring improves risk stratification in some strata of the population. OBJECTIVE: We evaluated individual and combined effects of reader experience, heart rate, vessel displacement, and trajectory on computed tomography (CT) Agatston score, calcium volume, and calcium mass in a cardiac phantom model. METHODS: A cardiac motion phantom was scanned with a 64-slice CT scanner with artificial electrocardiogram gating with combinations of the following: heart rates 60, 80, and 100 beat/min; vessel displacement of 1.25 and 2.5 cm; and multiple vessel trajectories of craniocaudal, right-left, anteroposterior, right coronary artery (RCA), left anterior descending, and left circumflex (LCX). Calcium quantification was done by 2 different readers with the use of 3 methods: Agatston, calcium volume, and calcium mass. RESULTS: Heart rate, coronary displacement, and trajectory had significant effects on all 3 techniques, with a general decrease in score as the heart rate increased. A vessel displacement of 2.5 cm decreased the Agatston score by 16% (P < 0.0001) and LCX motion decreased the score by 17% (P < 0.0001). Combined effects often resulted in larger differences; for example, a heart rate of 60 beat/min, vessel displacement of 1.25 cm, and RCA motion resulted in an Agatston score of 907, whereas with a heart rate of 100 beat/min, vessel displacement of 2.5 cm, and LCX motion the score was 604. CONCLUSION: The calcium score is affected by heart rate, vessel displacement, and trajectory.


Subject(s)
Coronary Angiography/instrumentation , Coronary Artery Disease/diagnostic imaging , Heart Rate , Multidetector Computed Tomography/instrumentation , Phantoms, Imaging , Vascular Calcification/diagnostic imaging , Artifacts , Coronary Angiography/methods , Coronary Artery Disease/physiopathology , Humans , Predictive Value of Tests , Reproducibility of Results , Vascular Calcification/physiopathology
18.
Virulence ; 2(1): 22-9, 2011.
Article in English | MEDLINE | ID: mdl-21224721

ABSTRACT

The early detection of invading viruses by the host depends on their identification by pathogen sensors. These include Toll-like receptors (TLRs) as well as cytoplasmic RNA helicases such as retinoic acid inducible protein I (RIG-I) and melanoma differentiation associated gene 5 (MDA-5). These pathogen sensors recognize specific molecular patterns found in viruses and trigger inflammatory and antiviral responses that result in the eradication of invading pathogens. In this study we investigated the specific recognition of Human rhinovirus 6 (HRV6) the common cold pathogen by the innate immune response in lung epithelial cells. Our experiments established that in the first stages on infection the TLRs play a crucial role in HRV recognition and that different constituents of HRV6 are recognized by different TLRs, while upon viral replication and generation of dsRNA the type I IFN inflammatory response is mediated by MDA-5. The HRV6 capsid is recognized via TLR2, whereas upon HRV6 ssRNA internalization the virus genome is recognized by TLR7 and TLR8. Upon generation of dsRNA the type I IFN response is mediated by MDA-5. The combined recognition by different TLRs and MDA5 and their upregulation concurs with the huge inflammatory response seen in the common cold caused by human rhinoviruses.


Subject(s)
DEAD-box RNA Helicases/immunology , Epithelial Cells/immunology , Picornaviridae Infections/immunology , Rhinovirus/immunology , Toll-Like Receptors/immunology , Cell Line , DEAD-box RNA Helicases/genetics , Epithelial Cells/virology , Humans , Immunity, Innate , Interferon Type I/immunology , Interferon-Induced Helicase, IFIH1 , Lung/immunology , Lung/virology , Picornaviridae Infections/virology , Rhinovirus/genetics , Rhinovirus/physiology , Toll-Like Receptors/genetics
19.
Am J Physiol Lung Cell Mol Physiol ; 286(4): L650-7, 2004 Apr.
Article in English | MEDLINE | ID: mdl-12818891

ABSTRACT

Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated cell are unknown. Cell ultrastructure analysis indicates ciliated cell commitment activates a multistage program involving synthesis of cilia precursor proteins and assembly of macromolecular complexes. Foxj1 is an f-box transcription factor expressed in ciliated cells and shown to be required for cilia formation by gene deletion in a mouse model. To identify a specific role for foxj1 in directing the ciliated cell phenotype, we evaluated the capacity of foxj1 to induce ciliogenesis and direct cilia assembly. In a primary culture model of wild-type mouse airway epithelial cells, foxj1 expression preceded the appearance of cilia and in cultured foxj1 null cells cilia did not develop. Delivery of foxj1 to polarized epithelial cell lines and primary cultured alveolar epithelial cells failed to promote ciliogenesis. Similarly, delivery of foxj1 to wild-type airway epithelial cells did not enhance the total number of ciliated cells. In contrast, delivery of foxj1 to null cells resulted in the appearance of cilia. Analysis revealed that, in the absence of foxj1, null cells contained cilia precursor basal bodies, indicating prior commitment to ciliogenesis. However, the basal bodies were disorganized within the apical compartment and failed to dock with the apical membrane. Reconstitution of foxj1 in null cells restored normal basal body organization, resulting in axoneme growth. Thus foxj1 functions in late-stage ciliogenesis to regulate programs promoting basal body docking and axoneme formation in cells previously committed to the ciliated cell phenotype.


Subject(s)
Cilia/physiology , DNA-Binding Proteins/genetics , Epithelial Cells/physiology , Epithelial Cells/ultrastructure , Respiratory Mucosa/cytology , Transcription Factors/genetics , Animals , Bronchi/cytology , Cell Differentiation , Cell Line , DNA-Binding Proteins/metabolism , Dogs , Forkhead Transcription Factors , Gene Expression , Humans , Kidney/cytology , Mice , Phenotype , Pulmonary Alveoli/cytology , Rats , Transcription Factors/metabolism
20.
J Cell Sci ; 116(Pt 24): 4935-45, 2003 Dec 15.
Article in English | MEDLINE | ID: mdl-14625387

ABSTRACT

Establishment and maintenance of epithelial cell polarity depend on cytoskeletal organization and protein trafficking to polarized cortical membranes. ERM (ezrin, radixin, moesin) family members link polarized proteins with cytoskeletal actin. Although ERMs are often considered to be functionally similar, we found that, in airway epithelial cells, apical localization of ERMs depend on cell differentiation and is independently regulated. Moesin was present in the apical membrane of all undifferentiated epithelial cells. However, in differentiated cells, ezrin and moesin were selectively localized to apical membranes of ciliated airway cells and were absent from secretory cells. To identify regulatory proteins required for selective ERM trafficking, we evaluated airway epithelial cells lacking Foxj1, an F-box factor that directs programs required for cilia formation at the apical membrane. Interestingly, Foxj1 expression was also required for localization of apical ezrin, but not moesin. Additionally, membrane-cytoskeletal and threonine-phosphorylated ezrin were decreased in Foxj1-null cells, consistent with absent apical ezrin. Although apical moesin expression was present in null cells, it could not compensate for ezrin because ERM-associated EBP50 and the beta2 adrenergic receptor failed to localize apically in the absence of Foxj1. These findings indicate that Foxj1 regulates ERM proteins differentially to selectively direct the apical localization of ezrin for the organization of multi-protein complexes in apical membranes of airway epithelial cells.


Subject(s)
Cell Polarity/physiology , DNA-Binding Proteins/metabolism , Epithelial Cells/metabolism , Microfilament Proteins/metabolism , Phosphoproteins/metabolism , Sodium-Hydrogen Exchangers , Trans-Activators/metabolism , Adenoviridae/metabolism , Animals , Carrier Proteins/metabolism , Cell Differentiation/physiology , Cell Membrane/metabolism , Cells, Cultured , Cilia/metabolism , Cytoskeletal Proteins , Cytoskeleton/metabolism , Epithelial Cells/cytology , Forkhead Transcription Factors , Immunohistochemistry , Mice , Phosphorylation , Protein Transport , Receptors, Adrenergic, beta-2/metabolism , Trachea/metabolism
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