18 results on '"Layliev J"'
Search Results
2. 30: SHIFTING CELLULAR REDOX BALANCE: TOPICAL SILENCING OF KEAP1 INCREASES ANTIOXIDANT CELLULAR PROTECTION, IMPROVING DIABETIC WOUND HEALING
- Author
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Cohen, O, primary, Patel, M, additional, Layliev, J, additional, Wetterau, M, additional, Szpalski, C, additional, Knobel, D, additional, Ceradini, DJ, additional, Warren, SM, additional, and Saadeh, PB, additional
- Published
- 2011
- Full Text
- View/download PDF
3. 72: HYPERGLYCEMIA AND ISCHEMIA IN DIABETES: STRESSORS IMPLICATED IN DYSFUNCTIONAL HEALING
- Author
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Knobel, D, primary, Cohen, O, additional, Crawford, JL, additional, Butala, P, additional, Layliev, J, additional, Wetterau, MT, additional, Warren, SM, additional, and Saadeh, PB, additional
- Published
- 2011
- Full Text
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4. 81: STEM CELL THERAPY IMPROVES BONY HEALING
- Author
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Layliev, J, primary, Marchac, A, additional, Butala, P, additional, Szpalski, C, additional, Henderson, R, additional, Sagepin, F, additional, Weinstein, A, additional, Saadeh, PB, additional, and Warren, SM, additional
- Published
- 2011
- Full Text
- View/download PDF
5. Induction and patterning of the Purkinje fibre network
- Author
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Mikawa, T., Gourdie, R.G., Takebayashi-Suzuki, K., Kanzawa, N., Hyer, J., Pennisi, D.J., Poma, C.P., Shulimovich, M., Diaz, K.G., Layliev, J., Prasad, A., Mikawa, T., Gourdie, R.G., Takebayashi-Suzuki, K., Kanzawa, N., Hyer, J., Pennisi, D.J., Poma, C.P., Shulimovich, M., Diaz, K.G., Layliev, J., and Prasad, A.
- Abstract
Impulse-conducting Purkinje cells differentiate from myocytes during embryogenesis. In the embryonic chicken heart, this conversion of contractile myocytes into conduction cells occurs subendocardially and periarterially. The unique sites of Purkinje fibre differentiation suggest that a shear stress-induced paracrine signal from the endocardium and arterial beds may induce adjacent myocytes to differentiate into conduction cells. Consistent with this model, Purkinje fibre marker genes can be induced in cultured embryonic myocytes by endothelin (ET), an endothelial cell-derived signalling peptide. This inductive response is, however, gradually lost from myocytes as embryos develop, and mature myocytes express only genes characteristic of hypertrophy in response to ET. In vivo, active ET is produced, through proteolytic processing, from its precursor by ET-converting enzyme 1 (ECE1) and triggers signalling by binding to its receptors, ETA and ETB. In the embryonic heart, the expression of these ET signalling components changes dynamically, defining the site and timing of Purkinje fibre differentiation within the ventricular myocardium during chick embryogenesis.
- Published
- 2003
6. Induction and patterning of the Purkinje fibre network
- Author
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Mikawa, T., Gourdie, R. G., Takebayashi-Suzuki, K., Kanzawa, N., Hyer, J., David Pennisi, Poma, C. P., Shulimovich, M., Diaz, K. G., Layliev, J., Prasad, A., Schiaffino, and Fishman
7. Excluding Antibiotics in the Management of Nonoperative Orbital and Zygomatic Fractures.
- Author
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Pessino K, Cook T, Layliev J, Bradley JP, and Bastidas N
- Subjects
- Anti-Bacterial Agents therapeutic use, Humans, Middle Aged, Orbit, Prospective Studies, Retrospective Studies, Orbital Fractures drug therapy, Zygomatic Fractures drug therapy
- Abstract
Introduction: Indications for prophylactic antibiotic therapy in nonoperative, closed fractures of the orbit and zygoma remain controversial and are based on anecdotal data. The purpose of this study was to report the incidence of infectious sequelae among patients who presented to our institution with stated fractures and who were not administered prophylactic antibiotic therapy. The authors hypothesized that an increase in infectious complications would not be seen in these patients., Methods: The authors conducted a prospective single site study from October 2015 to December 2019. Patients with closed, nonoperative fractures involving the orbit and/or zygoma were included. These patients did not receive prophylactic antibiotic therapy for their fracture patterns, and infectious complications including orbital cellulitis, meningitis, and bacterial sinusitis were noted if present during follow-up., Results: Of 301 patients with closed, nonoperative orbital and/or zygomatic fractures, 268 were included in the study and 33 were excluded because of administration of antibiotics. The average age was 60 years, and the most common mechanism of injury was a traumatic fall. Fracture types included 100 orbital wall, 133 orbital floor, 15 orbital rim, 23 orbital roof, 48 zygoma, and 44 zygomaticomaxillary compound fractures. Infectious sequelae were not identified in any patient., Conclusions: Of the 268 patients included in the study, no infectious complications were identified during the follow-up period. This outcome further supports that the use of prophylactic antibiotics is not indicated for closed, nonoperative fractures involving the orbital and/or zygoma. Prospective randomized control studies would be useful to support this outcome and better guide clinical antibiotic prescribing practices., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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8. Enhanced Recovery Pathway in Microvascular Autologous Tissue-Based Breast Reconstruction: Should It Become the Standard of Care?
- Author
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Kaoutzanis C, Ganesh Kumar N, O'Neill D, Wormer B, Winocour J, Layliev J, McEvoy M, King A, Braun SA, and Higdon KK
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Hospital Costs statistics & numerical data, Humans, Length of Stay economics, Length of Stay statistics & numerical data, Logistic Models, Middle Aged, Multivariate Analysis, Perioperative Care economics, Perioperative Care standards, Postoperative Complications economics, Postoperative Complications epidemiology, Postoperative Complications prevention & control, Retrospective Studies, Tennessee, Transplantation, Autologous, Young Adult, Free Tissue Flaps economics, Free Tissue Flaps transplantation, Mammaplasty economics, Mammaplasty methods, Perioperative Care methods, Standard of Care
- Abstract
Background: Enhanced recovery pathway programs have demonstrated improved perioperative care and shorter length of hospital stay in several surgical disciplines. The purpose of this study was to compare outcomes of patients undergoing autologous tissue-based breast reconstruction before and after the implementation of an enhanced recovery pathway program., Methods: The authors retrospectively reviewed consecutive patients who underwent autologous tissue-based breast reconstruction performed by two surgeons before and after the implementation of the enhanced recovery pathway at a university center over a 3-year period. Patient demographics, perioperative data, and 45-day postoperative outcomes were compared between the traditional standard of care (pre-enhanced recovery pathway) and enhanced recovery pathway patients. Multivariate logistic regression was performed to identify risk factors for length of hospital stay. Cost analysis was performed., Results: Between April of 2014 and January of 2017, 100 consecutive women were identified, with 50 women in each group. Both groups had similar demographics, comorbidities, and reconstruction types. Postoperatively, the enhanced recovery pathway cohort used significantly less opiate and more acetaminophen compared with the traditional standard of care cohort. Median length of stay was shorter in the enhanced recovery pathway cohort, which resulted in an extrapolated $279,258 savings from freeing up inpatient beds and increase in overall contribution margins of $189,342. Participation in an enhanced recovery pathway program and lower total morphine-equivalent use were independent predictors for decreased length of hospital stay. Overall 45-day major complication rates, partial flap loss rates, emergency room visits, hospital readmissions, and unplanned reoperations were similar between the two groups., Conclusion: Enhanced recovery pathway program implementation should be considered as the standard approach for perioperative care in autologous tissue-based breast reconstruction because it does not affect morbidity and is associated with accelerated recovery with reduced postoperative opiate use and decreased length of hospital stay, leading to downstream health care cost savings., Clinical Question/level of Evidence: Therapeutic, III.
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- 2018
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9. Incidence and Preoperative Risk Factors for Major Complications in Aesthetic Rhinoplasty: Analysis of 4978 Patients.
- Author
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Layliev J, Gupta V, Kaoutzanis C, Ganesh Kumar N, Winocour J, Grotting JC, and Higdon KK
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- Adolescent, Adult, Age Factors, Aged, Body Mass Index, Female, Hospitalization statistics & numerical data, Humans, Incidence, Lung Diseases etiology, Male, Middle Aged, Postoperative Complications etiology, Prospective Studies, Reoperation statistics & numerical data, Rhinoplasty methods, Risk Factors, Treatment Outcome, United States epidemiology, Young Adult, Esthetics, Lung Diseases epidemiology, Postoperative Complications epidemiology, Rhinoplasty adverse effects
- Abstract
Background: Rhinoplasty remains one of the most common aesthetic procedures performed in the United States. Current literature on rhinoplasty complications is inconclusive and is based on retrospective reviews and small cohorts., Objectives: The purpose of this study was to examine the incidence and identify predictive risk factors for major complications following rhinoplasty alone or in combination with other aesthetic operations in a large, prospective, multicenter database study., Methods: A prospective cohort of patients undergoing rhinoplasty between May 2008 and May 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications, defined as complications requiring an emergency room visit, hospital admission, or a reoperation within 30 days of the index operation. Univariate and multivariate analysis evaluated potential risk factors for major complications including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, and combined procedures., Results: A total of 129,007 patients were identified, of which 4978 (3.9%) underwent a rhinoplasty. The overall complication rate was 0.7% (n = 37). Hematoma was the most common complication (0.2%), followed by infection (0.2%), and pulmonary complications (0.1%). Age ≥40 years was found to be an independent risk factor for developing complications. Age ≥40 years was found to have a relative risk of 2.05 (P = 0.04) for any major complication. Complications increased from 0.58% in rhinoplasty alone cases to 1.02% (P < 0.05) with the addition of 1 other body region to 2.09% with the addition of 2 other body regions (P < 0.05). The risk of pulmonary complications increased from 0.1% to 1% (P < 0.05) with the addition of rhinoplasty with 2 other body regions. Gender, type of facility, smoking status, and BMI ≥25 did not appear to significantly impact the risk for major complications., Conclusions: The major complication rate following rhinoplasty remains low. The risk is increased with age ≥40 years and with the addition of other cosmetic procedures. Pulmonary complications, although rare, do occur, and also increase when combining rhinoplasty with other aesthetic surgery. These findings are important to consider when planning rhinoplasty and educating patients on the safety of combined aesthetic surgeries., Level of Evidence: 2., (© 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com)
- Published
- 2017
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10. Cosmetic Liposuction: Preoperative Risk Factors, Major Complication Rates, and Safety of Combined Procedures.
- Author
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Kaoutzanis C, Gupta V, Winocour J, Layliev J, Ramirez R, Grotting JC, and Higdon K
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Body Contouring methods, Chi-Square Distribution, Child, Child, Preschool, Databases, Factual, Female, Humans, Logistic Models, Male, Middle Aged, Obesity complications, Odds Ratio, Postoperative Complications therapy, Prospective Studies, Risk Factors, Time Factors, Treatment Outcome, United States, Young Adult, Body Contouring adverse effects, Lipectomy adverse effects, Postoperative Complications etiology
- Abstract
Background: Liposuction is among the most commonly performed aesthetic procedures, and is being performed increasingly as an adjunct to other procedures., Objectives: To report the incidence and risk factors of significant complications after liposuction, and to determine whether adding liposuction to other cosmetic surgical procedures impacts the complication risk., Methods: A prospective cohort of patients who underwent liposuction between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications requiring emergency room visit, hospital admission, or reoperation within 30 days of the operation. Univariate and multivariate analysis evaluated risk factors including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, and combined procedures., Results: Of the 31,010 liposuction procedures, only 11,490 (37.1%) were performed as a solitary procedure. Liposuction alone had a major complication rate of 0.7% with hematoma (0.15%), pulmonary complications (0.1%), infection (0.1%), and confirmed venous thromboembolism (VTE) (0.06%) being the most common. Independent predictors of major complications included combined procedures (Relative Risk (RR) 4.81), age (RR 1.01), BMI (RR 1.05), and procedures performed in hospitals (RR 1.36). When examining specifically other aesthetic procedures performed alone or with liposuction, combined procedures had a higher risk of confirmed VTE (RR 5.65), pulmonary complications (RR 2.72), and infection (RR 2.41), but paradoxically lower hematoma risk (RR 0.77) than solitary procedures., Conclusions: Liposuction performed alone is a safe procedure with a low risk of major complications. Combined procedures, especially on obese or older individuals, can significantly increase complication rates. The impact of liposuction on the risk of hematoma in combined procedures needs further investigation., (© 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com)
- Published
- 2017
- Full Text
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11. The Optimal Timing for Primary Cranial Vault Reconstruction in Nonsyndromic Craniosynostosis.
- Author
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Layliev J, Gill R, Spear M, Cifuentes J, Wang L, and Kelly KJ
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Male, Operative Time, Retrospective Studies, Craniosynostoses surgery, Orthopedic Procedures methods, Plastic Surgery Procedures methods, Skull surgery
- Abstract
There is a lack of consensus on the optimal timing for primary cranial vault reconstruction in cranial synostosis. The purpose of this study was to assess the impact of age at primary reconstruction on the need for revision surgery in nonsyndromic craniosynostosis. A retrospective review was conducted on all children undergoing cranial vault reconstruction for nonsyndromic craniosynostosis during a 10-year period. Demographics and length of follow-up was collected for each patient. Complications, mortality, need for reoperation, and type of reoperation were recorded. Reoperations were classified as total reoperations for premature reossification, voids and recontouring, just voids, and minor procedures. In total, 325 consecutive patients were included with an average length of follow-up of 3.3 years. The authors' complication rate was 11.1%, total reoperation rate was 26.8%, with zero mortalities. Sex and race did not impact the reoperation rate. Multiple suture synostoses were associated with increased risk of reoperation. A regression analysis showed that the lowest risk of reoperation occurred at an age of 200 days, with the 95% confidence interval of hazard ratios falling between 4 months and 8 months of age. Operation at earlier ages was associated with higher risk of reoperation for reossification, while operating at later ages was associated with higher risk for revision surgery to fill voids. Based on authors' institution's 10-year experience, authors' results suggest that the optimal timing for primary cranial vault reconstruction in nonsyndromic craniosynostosis is between 4 and 8 months. This operative window is associated with the lowest risk for revisionary surgery.
- Published
- 2016
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- View/download PDF
12. The certificate of added qualifications in microsurgery: consideration for subspecialty certification in microvascular surgery in the United States.
- Author
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Layliev J, Broer PN, Saadeh PB, Crisera CA, Wu LC, Boyd JB, Serletti JM, Levine JP, Roostaeian J, and Tanna N
- Subjects
- Humans, United States, Certification, Microsurgery, Specialties, Surgical
- Published
- 2015
- Full Text
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13. Endogenous cell therapy improves bone healing.
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Layliev J, Marchac A, Tanaka R, Szpalski C, Henderson R, Rubin MS, Saadeh PB, and Warren SM
- Subjects
- Animals, Benzylamines, Bone Regeneration drug effects, Cell Adhesion drug effects, Cell Movement drug effects, Cyclams, Disease Models, Animal, Flow Cytometry, Heterocyclic Compounds pharmacology, Humans, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic drug effects, Parathyroid Hormone pharmacology, Parietal Bone blood supply, Parietal Bone injuries, Recombinant Proteins therapeutic use, Stem Cells cytology, Cell- and Tissue-Based Therapy methods, Heterocyclic Compounds therapeutic use, Parathyroid Hormone therapeutic use, Stem Cells drug effects, Wound Healing drug effects
- Abstract
Background: Although bone repair is often a relatively rapid and efficient process, many bone defects do not heal. Because an adequate blood supply is essential for new bone formation, we hypothesized that augmenting new blood vessel formation by increasing the number of circulating vasculogenic progenitor cells (PCs) with AMD3100 and enhancing their trafficking to the site of injury with recombinant human parathyroid hormone (rhPTH) will improve healing., Methods: Critical-sized 3-mm cranial defects were trephined into the right parietal bone of C57BLKS/J 6 mice (N = 120). The mice were divided into 4 equal groups (n = 30 for each). The first group received daily subcutaneous injections of AMD3100 (5 mg/kg). The second group received daily subcutaneous injections of rhPTH (5 mg/kg). The third group received both AMD3100 and rhPTH. The fourth group received subcutaneous injections of saline. Circulating vasculogenic PC numbers, new blood vessel formation, and bony regeneration were assessed. Progenitor cell adhesion, migration, and tubule formation were assessed in the presence of rhPTH and AMD3100., Results: Flow cytometry demonstrated that combination therapy significantly increased the number of circulating PCs compared with all other groups. In vitro, AMD3100-treated PCs had significantly increased adhesion migration, and tubule formation was assessed in the presence of rhPTH. Combination therapy significantly improved new blood vessel formation in those with cranial defect compared with all other groups. Finally, bony regeneration was significantly increased in the combination therapy group compared with all other groups., Conclusions: The combination of a PC-mobilizing and traffic-enhancing agent improved bony regeneration of calvarial defects in mice.
- Published
- 2015
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14. Improving Wound Healing with Topical Gene Therapy.
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Layliev J, Wilson S, Warren SM, and Saadeh PB
- Abstract
Background: Impaired wound healing remains a major clinical problem with many etiologies. Altering gene expression to enhance healing is an innovative therapeutic approach. In recent years, we have developed a means to topically silence genes at the post-transcriptional level to locally alter wounds and improve the healing process., The Problem: Many types of chronic wounds have been associated with alterations in the expression of genes that mediate healing. Targeting the expression of these genes in a way that can improve healing while limiting systemic side effects has been very challenging., Basic/clinical Science Advances: Our laboratory's recent work has focused on the use of topically applied small interfering ribonucleic acid (siRNA) to inhibit messenger RNA expression of certain mediators involved in healing in two different types of cutaneous injury-radiation-induced cutaneous injury and the diabetic excisional wound. By successfully inhibiting specific gene mediators with topical siRNA, we reversed downstream signaling pathways, which led to expedited wound healing in diabetic wounds and restoration to a more normal phenotype in radiation-induced skin injuries., Clinical Care Relevance: The signaling pathways and gene mediators that we targeted and inhibited in murine models are present in humans. Applying parallel treatment strategies in humans may provide novel means of treating these burdensome and costly conditions., Conclusion: Our novel method for local gene silencing is effective in treating various types of cutaneous murine wounds. Topical gene silencing with siRNA obviates the side effects of systemic medication and has the potential to be effective in healing or preventing a wide array of cutaneous human conditions.
- Published
- 2012
- Full Text
- View/download PDF
15. Massive spontaneous hematoma from chronic enoxaparin (Lovenox) use.
- Author
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Mir T, Layliev J, and Glickman LT
- Subjects
- Acute Kidney Injury chemically induced, Acute Kidney Injury physiopathology, Acute Kidney Injury therapy, Anticoagulants therapeutic use, Combined Modality Therapy, Disease Progression, Dose-Response Relationship, Drug, Drainage methods, Enoxaparin therapeutic use, Female, Follow-Up Studies, Hematoma surgery, Humans, Middle Aged, Plastic Surgery Procedures methods, Severity of Illness Index, Shock, Hemorrhagic chemically induced, Shock, Hemorrhagic physiopathology, Shock, Hemorrhagic therapy, Treatment Outcome, Wound Healing physiology, Abdominal Wall, Anticoagulants adverse effects, Enoxaparin adverse effects, Hematoma chemically induced, Surgical Flaps
- Published
- 2010
- Full Text
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16. Nonoperative management of symptomatic urachal anomalies.
- Author
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Lipskar AM, Glick RD, Rosen NG, Layliev J, Hong AR, Dolgin SE, and Soffer SZ
- Subjects
- Adolescent, Algorithms, Child, Child, Preschool, Fistula diagnosis, Humans, Infant, Infant, Newborn, Retrospective Studies, Treatment Outcome, Urachal Cyst diagnosis, Fistula therapy, Urachal Cyst therapy, Urachus abnormalities
- Abstract
Introduction: Symptomatic urachal anomalies are rare disorders that consist of urachal remnants or fistulas with or without an associated cyst. Traditionally, when a urachal anomaly was recognized, operative excision was performed. There has been a shift toward the nonoperative management of urachal anomalies at many centers, although there is little in the literature to support this practice., Methods: A retrospective chart review of patients with urachal anomalies was performed from January 2002 to March 2008. Children with a draining umbilicus and no radiographic or surgical confirmation of a urachal anomaly were excluded., Results: Fifteen patients with symptomatic urachal anomalies were identified. The average age was 3.5 years (4 weeks to 14 years). Symptoms included umbilical drainage (n = 10), abdominal pain (n = 6), omphalitis (n = 4), intraabdominal mass (n = 3), dysuria (n = 1), recurrent urinary tract infections (n = 1), and fever (n = 4). The diagnosis was confirmed by ultrasound (n = 13) and/or computed tomographic scan (n = 4). The surgically treated cases included 7 urachal cysts (5 uninfected, 2 infected) and 1 patent urachal fistula. Mean follow-up is 37 months, and there have been no reported recurrences. Those treated without surgical excision included 4 patent urachal fistulas (mean follow-up, 20 months-no recurrences) and 3 infected urachal cysts (percutaneous drainage [n = 2] and laparoscopic drainage [n = 1]-no recurrences on ultrasound at 26 months)., Conclusion: Nonoperative management of urachal anomalies is a reasonable approach and may be extended to infected urachal cysts after initial drainage. Infected cysts that are adequately drained seem to obliterate with time. Modern ultrasonography facilitates thorough follow-up. We propose a treatment algorithm for the management of suspected urachal anomalies., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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17. Induction and patterning of the Purkinje fibre network.
- Author
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Mikawa T, Gourdie RG, Takebayashi-Suzuki K, Kanzawa N, Hyer J, Pennisi DJ, Poma CP, Shulimovich M, Diaz KG, Layliev J, and Prasad A
- Subjects
- Animals, Aspartic Acid Endopeptidases metabolism, Endothelin-Converting Enzymes, Endothelium cytology, Endothelium metabolism, Heart anatomy & histology, Heart physiology, Metalloendopeptidases, Morphogenesis, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Purkinje Fibers anatomy & histology, Purkinje Fibers physiology, Receptors, Endothelin metabolism, Cell Differentiation physiology, Embryonic Induction, Heart growth & development, Purkinje Fibers embryology
- Abstract
Impulse-conducting Purkinje cells differentiate from myocytes during embryogenesis. In the embryonic chicken heart, this conversion of contractile myocytes into conduction cells occurs subendocardially and periarterially. The unique sites of Purkinje fibre differentiation suggest that a shear stress-induced paracrine signal from the endocardium and arterial beds may induce adjacent myocytes to differentiate into conduction cells. Consistent with this model, Purkinje fibre marker genes can be induced in cultured embryonic myocytes by endothelin (ET), an endothelial cell-derived signalling peptide. This inductive response is, however, gradually lost from myocytes as embryos develop, and mature myocytes express only genes characteristic of hypertrophy in response to ET. In vivo, active ET is produced, through proteolytic processing, from its precursor by ET-converting enzyme 1 (ECE1) and triggers signalling by binding to its receptors, ETA and ETB. In the embryonic heart, the expression of these ET signalling components changes dynamically, defining the site and timing of Purkinje fibre differentiation within the ventricular myocardium during chick embryogenesis.
- Published
- 2003
18. Competency of embryonic cardiomyocytes to undergo Purkinje fiber differentiation is regulated by endothelin receptor expression.
- Author
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Kanzawa N, Poma CP, Takebayashi-Suzuki K, Diaz KG, Layliev J, and Mikawa T
- Subjects
- Animals, Cell Differentiation, Chick Embryo, Cloning, Molecular, Gene Expression Regulation, Developmental, Molecular Sequence Data, Myocardium cytology, Purkinje Fibers embryology, Receptor, Endothelin A, Receptor, Endothelin B, Receptors, Endothelin metabolism, Up-Regulation, Heart embryology, Purkinje Fibers cytology, Receptors, Endothelin genetics
- Abstract
Purkinje fibers of the cardiac conduction system differentiate from heart muscle cells during embryogenesis. In the avian heart, Purkinje fiber differentiation takes place along the endocardium and coronary arteries. To date, only the vascular cytokine endothelin (ET) has been demonstrated to induce embryonic cardiomyocytes to differentiate into Purkinje fibers. This ET-induced Purkinje fiber differentiation is mediated by binding of ET to its transmembrane receptors that are expressed by myocytes. Expression of ET converting enzyme 1, which produces a biologically active ET ligand, begins in cardiac endothelia, both arterial and endocardial, at initiation of conduction cell differentiation and continues throughout heart development. Yet, the ability of cardiomyocytes to convert their phenotype in response to ET declines as embryos mature. Therefore, the loss of responsiveness to the inductive signal appears not to be associated with the level of ET ligand in the heart. This study examines the role of ET receptors in this age-dependent loss of inductive responsiveness and the expression profiles of three different types of ET receptors, ET(A), ET(B) and ET(B2), in the embryonic chick heart. Whole-mount in situ hybridization analyses revealed that ET(A) was ubiquitously expressed in both ventricular and atrial myocardium during heart development, while ET(B) was predominantly expressed in the atrium and the left ventricle. ET(B2) expression was detected in valve leaflets but not in the myocardium. RNase protection assays showed that ventricular expression of ET(A) and ET(B) increased until Purkinje fiber differentiation began. Importantly, the levels of both receptor isotypes decreased after this time. Retrovirus-mediated overexpression of ET(A) in ventricular myocytes in which endogenous ET receptors had been downregulated, enhanced their responsiveness to ET, allowing them to differentiate into conduction cells. These results suggest that the developmentally regulated expression of ET receptors plays a crucial role in determining the competency of ventricular myocytes to respond to inductive ET signaling in the chick embryo.
- Published
- 2002
- Full Text
- View/download PDF
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