20 results on '"Roy MG"'
Search Results
2. Variants of MUC5AC Play a Role in the Development of Pulmonary Fibrosis.
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Burch, LH, primary, Wise, AL, additional, Garantziotis, S, additional, Evans, CM, additional, Adler, KA, additional, Speer, MC, additional, Steele, MP, additional, Brown, KK, additional, Loyd, JE, additional, Gudmundsson, G, additional, Groshong, SD, additional, Dickey, BF, additional, Herron, A, additional, Kervitsky, D, additional, Talbert, JL, additional, Markin, C, additional, Zhang, L, additional, Park, J, additional, Auerbach, S, additional, Crews, AL, additional, Slifer, SH, additional, Xu, H, additional, Potocky, CF, additional, Masinde, T, additional, Roy, MG, additional, Jancewicz, JM, additional, Schwarz, MI, additional, and Schwartz, DA, additional
- Published
- 2009
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3. Reliability of hand-held dynamometry in assessment of knee extensor strength after hip fracture.
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Roy MG and Doherty TJ
- Abstract
OBJECTIVES: To examine the reliability of hand-held dynamometry in assessing knee extensor strength in inpatients undergoing rehabilitation after hip fracture and to examine the discriminant validity of this measure. DESIGN: A total of 16 subjects (14 women; mean +/- SD, 79 +/- 7 yrs) undergoing inpatient rehabilitation after hip fracture volunteered to participate. Isometric knee extensor strength of the fractured and unfractured sides was determined with a hand-held dynamometer. Subjects were retested 1-2 days after the initial testing session. RESULTS: Test-retest intraclass correlation coefficients were high for both the fractured (0.91) and unfractured legs (0.90). A low coefficient of variation was observed for both the fractured (15.3%) and unfractured (14.7%) sides. The maximal knee extensor strength was significantly different when comparing the fractured (7.9 +/- 3 kg) and unfractured (15.6 +/- 4 kg) legs. When comparing test 1 and test 2 mean values for the fractured leg, the scores significantly differed (t = 3.14, P < 0.01), with 13 of 16 subjects scoring higher on test 2. CONCLUSIONS: Hand-held dynamometry is a reliable and valid tool for assessment of knee extensor strength after hip fracture. Reduced knee extensor strength in the fractured leg may be an important component limiting rehabilitation progress in these patients. [ABSTRACT FROM AUTHOR]
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- 2004
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4. A Curious Case of Autoimmunity, Pancytopenia, and Disseminated Intravascular Coagulation.
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Roy MG, Bagchi AS, Bagchi A, Pal AK, and Mukherjee C
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- Humans, Female, Young Adult, Autoimmunity, Pancytopenia diagnosis, Pancytopenia etiology, Disseminated Intravascular Coagulation diagnosis, Disseminated Intravascular Coagulation etiology
- Abstract
History and Examination: A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC)., Discussion: Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light., Conclusion: In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further., (© Journal of the Association of Physicians of India 2024.)
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- 2024
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5. Plastic surgeon closure is comparable to orthopedic closure when a perioperative optimization protocol is instituted for pediatric patients with neuromuscular scoliosis.
- Author
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Grush AE, Mohan VE, Roy MG, Burns HR, and Monson LA
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- Humans, Child, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Surgical Wound Infection prevention & control, Retrospective Studies, Scoliosis etiology, Orthopedics, Surgeons, Spinal Fusion adverse effects, Spinal Fusion methods
- Abstract
Background Context: Since 2015, plastic multilayer closure (PMC) has been gaining attraction due to improved wound healing outcomes for medically complex patients. Plastic multilayer closure has been readily used for complex spine surgery closures in patients susceptible to wound healing issues (ie, dehiscence, surgical site infection [SSI]). However, PMC requires extensive soft tissue manipulation compared with standard orthopedic spine surgeon closure (SOC) and can result in extended operative times, increased transfusion rates, and more frequent returns to the operating room., Purpose: From 2016 to 2019, our institution implemented a perioperative protocol designed to decrease postoperative complication rates in NMS patients. A retrospective cohort study was performed to determine if PMC imparted advantages over SOC above and beyond that from the perioperative protocol., Study Design/setting: Retrospective study at a single academic institution., Patient Sample: Eighty-one pediatric patients with neuromuscular scoliosis undergoing spinal fixation surgery., Outcome Measures: Postoperative wound complications such as surgical site infection, hematoma, and superficial/deep dehiscence were the main outcome measures. Respiratory and neuromuscular complications along with duration of surgery were also recorded., Methods: A retrospective review was conducted of NMS patients undergoing spinal fixation at a single academic pediatric hospital over 4 years. Cases were labeled as SOC (n=41) or PMC (n=40) based on the closure technique applied. Reported 90-day complications were evaluated as the primary outcome., Results: Of the 81 reviewed patients, 45 reported complications, roughly equal between the study groups. While we found no statistically significant differences in rates of postoperative complications or SSIs, SOC cases were 30 minutes shorter on average with fewer returns to the operating room for additional surgery., Conclusions: With the implementation of our perioperative protocol for NMS patients, PMC did not result in fewer complications than SOC but the surgeries did take longer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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6. Velopharyngeal Insufficiency Following Furlow Versus Straight Line Repair With Intravelar Veloplasty: A Single-institution Experience.
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Davis MJ, Roy MG, Burns HR, Yim N, Wilson KD, Moore EE, Buchanan EP, and Monson LA
- Abstract
Background: Measurements of postoperative velopharyngeal dysfunction (VPD) can be used to determine the efficacy of a palatoplasty operation. Hypernasality and audible nasal air emission are typical manifestations of VPD during speech. We aimed to longitudinally compare VPD outcomes in postpalatoplasty patients who underwent Furlow repair versus straight line repair with intravelar veloplasty (IVVP). Additionally, we examined the relationship between VPD outcomes and select pre-existing patient characteristics., Methods: Retrospective chart review was performed to identify primary palatoplasty patients treated from April 2012 to March 2021. Variables collected included gender, syndromic status, primary language, Veau cleft type, type of speech assessment, age at time of surgery, degree of hypernasality, presence of audible nasal air emission, and overall adequacy of velopharyngeal function. Pearson χ2 test and multivariable t tests were used to analyze variables. Logistic regression was used to control for statistically significant variables., Results: Of the 118 patients included, 38 received a Furlow procedure and 80 received a straight line with IVVP procedure. Audible nasal air emission was present in 57.3% of straight line with IVVP patients and 42.9% of Furlow patients, with no statistically significant difference between groups. Clinically significant hypernasality was present in 42.1% of straight line with IVVP patients and 22.9% of Furlow patients (P=0.05). Velopharyngeal function was classified as adequate in 63.5% of straight line with IVVP patients and 83.3% of Furlow patients (P=0.03). However, after stratifying by syndromic versus nonsyndromic status, there was no statistically significant difference between straight line with IVVP and Furlow patients for postoperative hypernasality and velopharyngeal function., Conclusions: This study suggests that there are no statistically significant differences between straight line with IVVP and Furlow palatoplasty techniques regarding speech outcomes including hypernasality, audible nasal air emission, and overall VP function. Furthermore, select patient characteristics such as gender, primary language, syndromic status, age at repair, and Veau cleft type do not significantly impact postoperative speech outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)
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- 2023
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7. The Immunogenicity of DENV1-4 ED3s Strongly Differ despite Their Almost Identical Three-Dimensional Structures and High Sequence Similarities.
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Islam MD, Sharmin T, Tipo IH, Saha A, Yesmin S, Roy MG, Brindha S, Kuroda Y, and Islam MM
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- Animals, Mice, Antibodies, Viral, Viral Envelope Proteins chemistry, Serogroup, Dengue Virus, Severe Dengue, Dengue prevention & control
- Abstract
The development of a dengue (DENV) vaccine remains challenging due to the heteroserotypic infection, which can result in a potentially deadly hemorrhagic fever or dengue shock syndrome, and only a tetravalent vaccine can overcome this issue. Here, we report the immunogenicity of DENV envelope protein domain 3 (ED3) from all four DENV serotypes (DENV1-4) in Swiss albino and BALB/c mice models. Firstly, we observed that despite having very similar sequences and structures, both the humoral and cellular immunogenicity of ED3s varied significantly, with strength ranging from DENV2 ED3 (2ED3)~3ED3 > 1ED3 > 4ED3, which was assessed through anti-ED3 IgG titers, and DENV1 ED3 (1ED3) > 2ED3~3ED3 > 4ED3 as determined by monitoring T-cell memory (CD44+CD62L+ T cells with IL-4 and IFN-γ expression). Secondly, anti-1ED3 sera cross-reacted with 2ED3 and 3ED3; anti-2ED3 and anti-3ED3 sera cross-reacted with each other, but anti-4ED3 was completely serotype-specific. The lack of reciprocity of anti-1ED3's cross-reaction was unanticipated. Such disparity in the ED3 responses and cross-reaction might underlie the appearance of hemorrhagic fever and dengue shock syndrome. Hence, the development of an ED3-based tetravalent subunit vaccine would require understanding the aforementioned disparities.
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- 2023
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8. Analysis of adolescent patient satisfaction and well-being following reduction mammaplasty using the BREAST-Q survey.
- Author
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Davis MJ, Roy MG, and Monson LA
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- Adolescent, Adult, Female, Humans, Quality of Life, Surveys and Questionnaires, Treatment Outcome, Mammaplasty, Patient Satisfaction
- Abstract
Background: While functional breast reduction surgery has been shown to lead to increased quality of life in adult patients, the effects of this operation has not been investigated as thoroughly in adolescent patients. This study uses the BREAST-Q, a validated, surgery-specific questionnaire, to measure changes in adolescent patient well-being and satisfaction following reduction mammaplasty., Methods: All patients presenting for breast reduction consultation between February and December 2016 were asked to complete the BREAST-Q. Post-operative surveys were completed at three-month follow up. A matched control cohort was established using patients who completed a pre-operative survey and were deemed appropriate surgical candidates, but then were denied by insurance and did not undergo surgery., Results: Of the 28 adolescent patients who presented for breast reduction consultation, 15 met inclusion criteria; 11 patients underwent reduction mammaplasty, and 4 patients were included in the control cohort. When these groups were compared, statistically significant improvements were observed in all BREAST-Q categories except for sexual well-being. Overall patient satisfaction correlated most highly to satisfaction with information., Conclusions: This study examines quality of life outcomes in adolescent breast reduction patients using the BREAST-Q survey. Our findings indicate that adolescent patients have an improved quality of life following breast reduction, but that their satisfaction stems from different sources from those of adult patients. Further characterization of outcomes specific to young patients with surgically managed symptomatic macromastia will increase the practice of tailored, evidence-based medicine for adolescent patients., Level of Evidence: Treatment Study, Level III., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)
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- 2022
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9. Family satisfaction with telemedicine follow-up after pediatric plastic surgery.
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Roy MG, Dinnell DEG, Sequitin JD, Davies LW, and Tung JS
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- Child, Follow-Up Studies, Humans, Patient Satisfaction, Personal Satisfaction, Surgery, Plastic, Telemedicine
- Abstract
Objective: One issue faced at institutions that serve a vast area is patients' ability to travel for perioperative care. Telemedicine is an innovative way of providing care while removing the inconvenience of travel or the hindrance of cost associated with travel. We initiated telemedicine as an option for certain postoperative encounters and assessed patient family satisfaction with this novel approach., Methods: Our practice offers telemedicine visits to patients who have had simple surgical procedures, identified by a fixed list of CPT codes. Visits are scheduled 7 to 14 days after surgery. Families completed a satisfaction survey after their encounter., Results: A pilot program was initiated from January 2019 to March 2020 using this method of postoperative follow-up. The initial response from families (N = 60) was extremely positive., Conclusion: We anticipate the option for telemedicine visits will make postoperative follow-ups more amendable to families, increase adherence rates, and increase access to care., (Copyright © 2022 American Academy of Physician Assistants.)
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- 2022
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10. Furlow versus straight line repair with intravelar veloplasty: A 7-year single institution experience.
- Author
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Zietsman MS, Roy MG, Dibbs RP, Davis MJ, Wilson KD, Buchanan EP, and Monson LA
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- Humans, Infant, Palate, Soft surgery, Retrospective Studies, Treatment Outcome, Plastic Surgery Procedures
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- 2021
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11. Factors associated with delayed presentation of patients with craniosynostosis.
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Roy MG, Beh HZ, Ferry AM, Dibbs RP, and Monson LA
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- Humans, Retrospective Studies, Craniosynostoses
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- 2021
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12. Cleft Care Packages and the Impact on Postoperative Care Following a Primary Cleft Lip Repair.
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Roy MG, Davies LA, Guillen DE, Sequitin JD, Buchanan EP, Maricevich RS, Truong TA, and Monson LA
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- Child, Cicatrix, Humans, Infant, Postoperative Care, Postoperative Period, Cleft Lip surgery, Cleft Palate surgery
- Abstract
Objective: To provide caregivers with all the resources needed to care for a surgical site following a primary cleft lip repair and evaluate its efficacy on postoperative care., Setting/participants: Caregivers of infants ages 3 to 6 months with a cleft lip and/or palate undergoing a primary repair at the Texas Children's Hospital., Methods: Packages were given to caregivers at discharge following repair. Packages included instructions and supplies needed for surgical site care. At discharge an advanced practice provider obtained informed consent and a questionnaire that established baseline knowledge of surgical site care. Following the questionnaire, the advanced practice provider demonstrated how to care for the site using the package provided. Assessment of scar healing, nasal stent compliance, and ease of care was evaluated at postoperative follow up., Results: Thirty-two families were enrolled in this study. Our data supports that caregivers who are provided resources to care for the site had increased comfort level, preparedness, and compliance rates following a primary cleft lip repair. Eighty-four percent of respondents strongly agreed that the package provided aided in preparedness for site care with 100% of respondents recommending the resources to future families undergoing a cleft lip repair., Conclusions: Caregivers feel comfortable and equipped with their ability to care for their child's repaired cleft lip when given the appropriate instructions and supplies. In addition, they would recommend the packages to future families following a repair. Empowering families to be proactive in postoperative care will potentially lead to better outcomes in cleft care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)
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- 2021
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13. Orthognathic Surgical Treatment in a Patient With Hyperimmunoglobulin E Syndrome.
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Dibbs R, Raghuram A, Roy MG, Kaufman MG, and Monson LA
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- Adolescent, Humans, Job Syndrome complications, Male, Malocclusion, Angle Class III complications, Malocclusion, Angle Class III surgery, Mandible surgery, Maxilla surgery, Orthognathic Surgical Procedures, Treatment Outcome, Job Syndrome surgery
- Abstract
Autosomal-dominant hyperimmunoglobulin E syndrome (HIES), or Job syndrome, is a rare, multisystem, primary immunodeficiency disorder. Additionally, patients may also suffer from connective tissue, dental, and bone malformations. While current management of HIES is directed at prophylactic antibiotics to prevent infections, there is limited work describing surgical considerations for these patients, particularly with respect to hardware placement. Here we report a case of a patient with HIES who underwent orthognathic surgery for maxillary advancement and mandibular setback to address his severe class III malocclusion. The patient's postoperative course was complicated by significant infection, requiring multiple operations and ultimately, hardware removal after bone healing. Although this patient ultimately had a good outcome, the role of orthognathic surgery with implant placement in patients with HIES should be approached with caution and careful consideration.
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- 2020
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14. The polymeric mucin Muc5ac is required for allergic airway hyperreactivity.
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Evans CM, Raclawska DS, Ttofali F, Liptzin DR, Fletcher AA, Harper DN, McGing MA, McElwee MM, Williams OW, Sanchez E, Roy MG, Kindrachuk KN, Wynn TA, Eltzschig HK, Blackburn MR, Tuvim MJ, Janssen WJ, Schwartz DA, and Dickey BF
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- Allergens chemistry, Animals, Aspergillus oryzae chemistry, Asthma metabolism, Female, Immunohistochemistry, Inflammation, Lung metabolism, Male, Methacholine Chloride chemistry, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Mucus metabolism, Ovalbumin chemistry, Species Specificity, Bronchial Hyperreactivity metabolism, Mucin 5AC metabolism
- Abstract
In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.
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- 2015
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15. Muc5b is required for airway defence.
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Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O'Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, and Evans CM
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- Animals, Asthma immunology, Asthma metabolism, Bacterial Infections immunology, Bacterial Infections microbiology, Cilia physiology, Ear, Middle immunology, Ear, Middle microbiology, Female, Inflammation pathology, Lung metabolism, Lung microbiology, Macrophages immunology, Macrophages pathology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Mucin 5AC deficiency, Mucin 5AC metabolism, Mucin-5B deficiency, Mucin-5B genetics, Phagocytosis, Pulmonary Disease, Chronic Obstructive immunology, Pulmonary Disease, Chronic Obstructive microbiology, Staphylococcus aureus immunology, Survival Analysis, Lung immunology, Mucin-5B metabolism, Respiratory Mucosa immunology, Respiratory Mucosa metabolism
- Abstract
Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.
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- 2014
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16. Strain-dependent genomic factors affect allergen-induced airway hyperresponsiveness in mice.
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Kelada SN, Wilson MS, Tavarez U, Kubalanza K, Borate B, Whitehead GS, Maruoka S, Roy MG, Olive M, Carpenter DE, Brass DM, Wynn TA, Cook DN, Evans CM, Schwartz DA, and Collins FS
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- Airway Resistance genetics, Animals, Arthropod Proteins, Asthma immunology, Asthma physiopathology, Bronchial Hyperreactivity immunology, Bronchial Hyperreactivity physiopathology, Bronchial Provocation Tests, Bronchoconstriction drug effects, Bronchoconstrictor Agents, Cysteine Endopeptidases, Cytokines metabolism, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Immunoglobulin E blood, Immunoglobulin G blood, Lung physiopathology, Male, Methacholine Chloride, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mucins metabolism, Phenotype, Receptors, G-Protein-Coupled genetics, Th2 Cells immunology, Time Factors, Allergens, Antigens, Dermatophagoides immunology, Asthma genetics, Bronchial Hyperreactivity genetics, Bronchoconstriction genetics, Lung immunology
- Abstract
Asthma is etiologically and clinically heterogeneous, making the genomic basis of asthma difficult to identify. We exploited the strain-dependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with Der p 1. Allergic inflammation, serum antibody titers, mucous metaplasia, and airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to allergen challenge. Der p 1-challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and inflammation, but exhibited an unexpected decrease in airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several G-protein-coupled receptors involved in airway smooth muscle contraction, most notably the M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the protein level after challenge with Der p 1. Murine strain-dependent genomic responses in the lung offer insights into the different biological pathways that develop after allergen challenge. This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the down-modulation of expression of G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation.
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- 2011
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17. Mucin production during prenatal and postnatal murine lung development.
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Roy MG, Rahmani M, Hernandez JR, Alexander SN, Ehre C, Ho SB, and Evans CM
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- Animals, Female, Homeostasis, Immunohistochemistry methods, Lung metabolism, Mice, Mice, Inbred C57BL, Models, Biological, Mucin 5AC biosynthesis, Mucin-5B biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Gene Expression Regulation, Developmental, Lung embryology, Lung growth & development, Mucins metabolism
- Abstract
Mucus is a protective gel that lines respiratory tract surfaces. To identify potential roles for secreted gel--forming mucins in lung development, we isolated murine lungs on embryonic days (E) 12.5-18.5, and postnatal days (PN) days 5, 14, and 28. We measured the mucin gene expression by quantitative RT-PCR, and localization by histochemical and immunohistochemical labeling. Alcian blue/periodic acid--Schiff--positive cells are present from E15.5 through PN28. Muc5b transcripts were abundant at all time points from E14.5 to PN28. By contrast, transcript levels of Muc5ac and Muc2 were approximately 300 and 85,000 times lower, respectively. These data are supported by immunohistochemical studies demonstrating the production and localization of Muc5ac and Muc5b protein. This study indicates that mucin production is prominent in developing murine lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs.
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- 2011
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18. A common MUC5B promoter polymorphism and pulmonary fibrosis.
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Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, and Schwartz DA
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- Aged, Case-Control Studies, Female, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Lung metabolism, Male, Middle Aged, Mucin-5B metabolism, Mutation, Promoter Regions, Genetic, Chromosomes, Human, Pair 11, Idiopathic Pulmonary Fibrosis genetics, Lung Diseases, Interstitial genetics, Mucin-5B genetics, Polymorphism, Single Nucleotide
- Abstract
Background: The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk., Methods: Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families. We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression was assessed in lung tissue., Results: Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes. The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P=1.2×10(-15); allelic association with idiopathic pulmonary fibrosis, P=2.5×10(-37)). The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 6.8 (95% confidence interval [CI], 3.9 to 12.0) and 20.8 (95% CI, 3.8 to 113.7), respectively, for familial interstitial pneumonia and 9.0 (95% CI, 6.2 to 13.1) and 21.8 (95% CI, 5.1 to 93.5), respectively, for idiopathic pulmonary fibrosis. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 37.4 times as high as in unaffected subjects homozygous for the wild-type allele, P<0.001). MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis., Conclusions: A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis. Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis. (Funded by the National Heart, Lung, and Blood Institute and others.).
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- 2011
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19. Public sector administration of ecological economics systems using mediated modeling.
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van den Belt M, Kenyan JR, Krueger E, Maynard A, Roy MG, and Raphael I
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- Economic Competition economics, Humans, Models, Theoretical, Organizations economics, Organizations organization & administration, Organizations, Nonprofit economics, Organizations, Nonprofit organization & administration, Population Dynamics, Private Sector economics, Staff Development economics, Staff Development organization & administration, State Medicine economics, State Medicine organization & administration, Developing Countries economics, Economic Competition organization & administration, Public Sector economics
- Abstract
In today's climate of government outsourcing and multiple stakeholder involvement in public sector management and service delivery, it is more important than ever to rethink and redesign the structure of how policy decisions are made, implemented, monitored, and adapted to new realities. The traditional command-and-control approach is now less effective because an increasing amount of responsibility to deliver public goods and services falls on networks of nongovernment agencies. Even though public administrators are seeking new decision-making models in an increasingly more complex environment, the public sector currently only sparsely utilizes Mediated Modeling (MM). There is growing evidence, however, that by employing MM and similar tools, public interest networks can be better equipped to deal with their long-term viability while maintaining the short-term needs of their clients. However, it may require a shift in organizational culture within and between organizations to achieve the desired results. This paper explores the successes and barriers to implementing MM and similar tools in the public sector and offers insights into utilizing them through a review of case studies and interdisciplinary literature. We aim to raise a broader interest in MM and similar tools among public sector administrators at various administrative levels. We focus primarily, but not exclusively, on those cases operating at the interface of ecology and socio-economic systems.
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- 2010
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20. Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements.
- Author
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Young HW, Williams OW, Chandra D, Bellinghausen LK, Pérez G, Suárez A, Tuvim MJ, Roy MG, Alexander SN, Moghaddam SJ, Adachi R, Blackburn MR, Dickey BF, and Evans CM
- Subjects
- 3T3 Cells, Amino Acid Sequence, Animals, Antigens administration & dosage, Base Sequence, Cell Line, Conserved Sequence, DNA Primers genetics, Female, Humans, Lung immunology, Metaplasia, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mucin 5AC, Mucous Membrane pathology, Mucous Membrane physiopathology, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Messenger metabolism, Sequence Homology, Amino Acid, Up-Regulation, Lung pathology, Lung physiopathology, Mucins genetics, Mucins physiology
- Abstract
Mucus hypersecretion contributes to morbidity and mortality in many obstructive lung diseases. Gel-forming mucins are the chief glycoprotein components of airway mucus, and elevated expression of these during mucous metaplasia precedes the hypersecretory phenotype. Five orthologous genes (MUC2, MUC5AC, MUC5B, MUC6, and MUC19) encode the mammalian gel-forming mucin family, and several have been implicated in asthma, cystic fibrosis, and chronic obstructive pulmonary disease pathologies. However, in the absence of a comprehensive analysis, their relative contributions remain unclear. Here, we assess the expression of the entire gel-forming mucin gene family in allergic mouse airways and show that Muc5ac is the predominant gel-forming mucin induced. We previously showed that the induction of mucous metaplasia in ovalbumin-sensitized and -challenged mouse lungs occurs within bronchial Clara cells. The temporal induction and localization of Muc5ac transcripts correlate with the induced expression and localization of mucin glycoproteins in bronchial airways. To better understand the tight regulation of Muc5ac expression, we analyzed all available 5'-flanking sequences of mammalian MUC5AC orthologs and identified evolutionarily conserved regions within domains proximal to the mRNA coding region. Analysis of luciferase reporter gene activity in a mouse transformed Clara cell line demonstrates that this region possesses strong promoter activity and harbors multiple conserved transcription factor-binding motifs. In particular, SMAD4 and HIF-1alpha bind to the promoter, and mutation of their recognition motifs abolishes promoter function. In conclusion, Muc5ac expression is the central event in antigen-induced mucous metaplasia, and phylogenetically conserved 5' noncoding domains control its regulation.
- Published
- 2007
- Full Text
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