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Allen F Ryan - One of the best experts on this subject based on the ideXlab platform.

  • both canonical and non canonical nf κb activation contribute to the proliferative response of the Middle Ear Mucosa during bacterial infection
    2016
    Co-Authors: Nicholas J G Webster, Arwa Kurabi, Allen F Ryan
    Abstract:

    A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the Middle Ear Mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in Mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated Mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of Mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured Mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of...

  • both canonical and non canonical nf κb activation contribute to the proliferative response of the Middle Ear Mucosa during bacterial infection
    2016
    Co-Authors: Chang Gun Cho, Kwang Pak, Nicholas J G Webster, Arwa Kurabi, Allen F Ryan
    Abstract:

    A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the Middle Ear Mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in Mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated Mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of Mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured Mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-κB activation dominates Mucosal hyperplasia during OM.

  • role of p38 mitogen activated protein kinase in Middle Ear Mucosa hyperplasia during bacterial otitis media
    2004
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Darrell Austen, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of the Middle Ear Mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in Middle Ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the Middle Ear Mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat Middle Ear Mucosal hyperplasia in which Mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic Mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated Mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the Middle Ear Mucosa during bacterial otitis media.

  • participation of ras and extracellular regulated kinase in the hyperplastic response of Middle Ear Mucosa during bacterial otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of Middle-Ear Mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the Middle Ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.

  • growth factors and their receptors in the Middle Ear Mucosa during otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Thecla Bennett, Allen F Ryan
    Abstract:

    Objective: The hyperplastic response of the Middle Ear Mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors. The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the Middle Ear Mucosa during otitis media. Study Design: Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat Middle Ear with bacteria. Methods: The Middle Ears of 12 male Sprague-Dawley rats were injected with 10 5 /mL Haemophilus influenzae strain 3655 (nontypeable, biotype II). Three rats were killed at 6, 24, 48, and 72 hours. Three untreated rats were also killed to serve as negative controls. The Middle Ear Mucosa samples were surgically removed and homogenized. Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor , hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-a. Results: Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal Middle Ear Mucosa. Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested. Betacellulin and neuregulin-a products were present at all time points except 72 hours after infection. Conclusions: The results of the study support a role for growth factors in the Middle Ear Mucosa during otitis media. These bioactive ingredients contribute to Mucosal hyperplasia.

Sean D Palacios - One of the best experts on this subject based on the ideXlab platform.

  • role of p38 mitogen activated protein kinase in Middle Ear Mucosa hyperplasia during bacterial otitis media
    2004
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Darrell Austen, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of the Middle Ear Mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in Middle Ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the Middle Ear Mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat Middle Ear Mucosal hyperplasia in which Mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic Mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated Mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the Middle Ear Mucosa during bacterial otitis media.

  • participation of ras and extracellular regulated kinase in the hyperplastic response of Middle Ear Mucosa during bacterial otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of Middle-Ear Mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the Middle Ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.

  • growth factors and their receptors in the Middle Ear Mucosa during otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Thecla Bennett, Allen F Ryan
    Abstract:

    Objective: The hyperplastic response of the Middle Ear Mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors. The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the Middle Ear Mucosa during otitis media. Study Design: Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat Middle Ear with bacteria. Methods: The Middle Ears of 12 male Sprague-Dawley rats were injected with 10 5 /mL Haemophilus influenzae strain 3655 (nontypeable, biotype II). Three rats were killed at 6, 24, 48, and 72 hours. Three untreated rats were also killed to serve as negative controls. The Middle Ear Mucosa samples were surgically removed and homogenized. Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor , hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-a. Results: Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal Middle Ear Mucosa. Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested. Betacellulin and neuregulin-a products were present at all time points except 72 hours after infection. Conclusions: The results of the study support a role for growth factors in the Middle Ear Mucosa during otitis media. These bioactive ingredients contribute to Mucosal hyperplasia.

  • growth factors influence growth and differentiation of the Middle Ear Mucosa
    2001
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Heinz Oehl, Christoph Aletsee, Allen F Ryan
    Abstract:

    Objective Otitis media is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by Mucosal hyperplasia that is thought to be mediated by the complex actions of growth factors and their respective receptors. It was the purpose of this study to determine which growth factors might be responsible for the growth and differentiation of the Middle Ear epithelium during otitis media. Study Design The effect of several growth factors on the expansion and differentiation of normal Middle Ear Mucosa was evaluated in tissue culture. Materials and Methods Explants of normal rat Middle Ear Mucosa were exposed in vitro to six different growth factors known to influence epithelial cells in other tissues: epidermal growth factor, amphiregulin, betacellulin, heregulin-α, keratinocyte growth factor, and hepatocyte growth factor. Results After 12 days, the growth and level of cytokeratin expression were analyzed for each of the explant outgrowths. Each factor appEared to have a significant, concentration-dependent effect on either the growth or differentiation of the cultured Middle Ear epithelial cells. Conclusion The results suggest that several of the tested growth factors may play a significant role in controlling hyperplasia of the Middle Ear Mucosa during otitis media.

Kwang Pak - One of the best experts on this subject based on the ideXlab platform.

  • both canonical and non canonical nf κb activation contribute to the proliferative response of the Middle Ear Mucosa during bacterial infection
    2016
    Co-Authors: Chang Gun Cho, Kwang Pak, Nicholas J G Webster, Arwa Kurabi, Allen F Ryan
    Abstract:

    A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the Middle Ear Mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in Mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated Mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of Mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured Mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-κB activation dominates Mucosal hyperplasia during OM.

  • role of p38 mitogen activated protein kinase in Middle Ear Mucosa hyperplasia during bacterial otitis media
    2004
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Darrell Austen, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of the Middle Ear Mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in Middle Ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the Middle Ear Mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat Middle Ear Mucosal hyperplasia in which Mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic Mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated Mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the Middle Ear Mucosa during bacterial otitis media.

  • participation of ras and extracellular regulated kinase in the hyperplastic response of Middle Ear Mucosa during bacterial otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of Middle-Ear Mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the Middle Ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.

  • growth factors and their receptors in the Middle Ear Mucosa during otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Thecla Bennett, Allen F Ryan
    Abstract:

    Objective: The hyperplastic response of the Middle Ear Mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors. The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the Middle Ear Mucosa during otitis media. Study Design: Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat Middle Ear with bacteria. Methods: The Middle Ears of 12 male Sprague-Dawley rats were injected with 10 5 /mL Haemophilus influenzae strain 3655 (nontypeable, biotype II). Three rats were killed at 6, 24, 48, and 72 hours. Three untreated rats were also killed to serve as negative controls. The Middle Ear Mucosa samples were surgically removed and homogenized. Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor , hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-a. Results: Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal Middle Ear Mucosa. Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested. Betacellulin and neuregulin-a products were present at all time points except 72 hours after infection. Conclusions: The results of the study support a role for growth factors in the Middle Ear Mucosa during otitis media. These bioactive ingredients contribute to Mucosal hyperplasia.

  • growth factors influence growth and differentiation of the Middle Ear Mucosa
    2001
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Heinz Oehl, Christoph Aletsee, Allen F Ryan
    Abstract:

    Objective Otitis media is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by Mucosal hyperplasia that is thought to be mediated by the complex actions of growth factors and their respective receptors. It was the purpose of this study to determine which growth factors might be responsible for the growth and differentiation of the Middle Ear epithelium during otitis media. Study Design The effect of several growth factors on the expansion and differentiation of normal Middle Ear Mucosa was evaluated in tissue culture. Materials and Methods Explants of normal rat Middle Ear Mucosa were exposed in vitro to six different growth factors known to influence epithelial cells in other tissues: epidermal growth factor, amphiregulin, betacellulin, heregulin-α, keratinocyte growth factor, and hepatocyte growth factor. Results After 12 days, the growth and level of cytokeratin expression were analyzed for each of the explant outgrowths. Each factor appEared to have a significant, concentration-dependent effect on either the growth or differentiation of the cultured Middle Ear epithelial cells. Conclusion The results suggest that several of the tested growth factors may play a significant role in controlling hyperplasia of the Middle Ear Mucosa during otitis media.

K Prellner - One of the best experts on this subject based on the ideXlab platform.

  • increased secretory capacity of the Middle Ear Mucosa after acute otitis media caused by haemophilus influenzae type b
    1997
    Co-Authors: Per Cayethomasen, Ann Hermansson, Mirko Tos, K Prellner
    Abstract:

    Abstract Secretory otitis media is associated with a highly increased goblet cell density of the Middle Ear Mucosa. Previous studies have shown that a single episode of experimental acute otitis media caused by Streptococcus pneumoniae or nontypeable Haemophilus influenzae is followed by increased goblet cell density for a period of at least 6 months. This condition may create a predisposition for subsequent development of secretory otitis media. We inoculated the Middle Ears of 25 rats with type B H. influenzae to determine the effect of the bacteria on Mucosal secretory capacity. Five rats were euthanized 4, 8, 16, 60, and 180 days after inoculation, followed by dissection, staining, and whole-mount embedding of the Middle Ear Mucosa. The goblet cell density was determined in 24 well-defined localities. Compared with that of 25 normal Middle Ears, the goblet cell density was significantly increased in almost all counting localities on all days of euthanasia. Thus increased goblet cell density and enlargement of Mucosal areas containing goblet cells persisted for 6 months after the acute incident. Inoculation of type B H. influenzae induced an increase of goblet cell density that was higher than the increase after inoculation of S. pneumoniae or nontypeable H. influenzae . We conclude that experimental acute otitis media caused by type B H. influenzae is followed by a longstanding increase of Mucosal secretory capacity, which is likely to induce a subsequent development of secretory otitis media. (Otolaryngol Head Neck Surg 1997;117:263-7.)

  • penicillin reduces secretory capacity in rat Middle Ear Mucosa in acute otitis media
    1996
    Co-Authors: Per Cayethomasen, A Hermansson, Mirko Tos, K Prellner
    Abstract:

    In the United States, antibiotic treatment of acute otitis media is almost mandatory, whereas several other western countries are more reticent. Most clinical trails on antibiotic effect have important methodologic flaws, making an overall interpretation quite difficult. This study determined the effect of penicillin V administration on the secretory capacity of rat Middle Ear Mucosa, during and after acute pneumococcal otitis media, by quantitative studies of the goblet cell density. The right Middle Ear bullae of 25 rats were inoculated with type 3 pneumococci. Beginning 2 days after inoculation, penicillin V 100 mg/kg/day was administered orally for 5 days. After inoculation, five randomly selected rats were killed on days 4, 8, 16, 90, and 180. The Middle Ear bullae were removed, split in half, stained with periodic acid-Schiff (PAS)-alcian blue, and the Mucosae dissected from the bone. Whole mounts were prepared and the goblet cell density determined in 24 well-defined localities, making a total of 160 counts per Ear and covering the entire bulla Mucosa. Goblet cell densities were compared with those of 25 normal Ears and 25 inoculated, untreated Ears. Except on day 4, the penicillin V-treated Ears had a significantly lower goblet cell density in almost all localities, on all days of death, when compared with untreated Ears. Six months after the acute incident, the goblet cell density was almost normal. However, the enlargement of the Mucosal area containing goblet cells seen in untreated Ears was unaffected by penicillin V administration. We conclude that administration of penicillin V reduces the increase in secretory capacity of rat Middle Ear Mucosa during and 6 months after acute pneumococcal otitis media.

  • changes in goblet cell density in rat Middle Ear Mucosa in acute otitis media
    1995
    Co-Authors: Per Cayethomasen, A Hermansson, Mirko Tos, K Prellner
    Abstract:

    This study was undertaken to determine quantitative histologic changes after a single episode of acute suppurative otitis media in the rat Middle Ear Mucosa, with special reference to goblet cell density, and to determine the persistency of these changes. Drum vascularization, purulent effusion, Mucosal thickness, bone and subepithelial gland formation was assessed. Twenty-five rats were inoculated with viable pneumococci type 3 through the right, bony Middle Ear bulla. The left bulla served as control. At days 4, 8, 16, 90, and 180 after inoculation, five rats were sacrificed on each occasion; the bullae were removed, opened, and divided into two halves, which were stained according to the periodic acid-Schiff (PAS)-alcian blue method. The stained Mucosa was dissected from the bone and placed in an anise oil-colophonium chamber, for determination of interindividual median density and range of goblet cells by light microscopy. Counting was performed in 24 well-defined localities, covering the entire bulla Mucosa and the drum. Areas normally containing goblet cells were extended. Goblet cell density was significantly (Mann-Whitney, p < .05) increased in almost all localities, reaching a maximum at day 16, whereafter the Mucosa normalized. All changes quantitated, except drum vascularization and purulent effusion, were persisting at day 180. Cobblestone appEarance of the epithelial surface and polypous Mucosal prominences were found. Mucosal thickening was prominent in areas covered with flat epithelium, less so in other areas. Local differences in the degree of increased Mucosal thickness were preventing intrinsic tubal occlusion. Enhanced secretory ability of the Middle Ear Mucosa was persisting 6 months after a single episode of acute suppurative otitis media, perhaps predisposing secretory otitis media.

Alexander Z Rivkin - One of the best experts on this subject based on the ideXlab platform.

  • role of p38 mitogen activated protein kinase in Middle Ear Mucosa hyperplasia during bacterial otitis media
    2004
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Darrell Austen, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of the Middle Ear Mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in Middle Ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the Middle Ear Mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat Middle Ear Mucosal hyperplasia in which Mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic Mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated Mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the Middle Ear Mucosa during bacterial otitis media.

  • participation of ras and extracellular regulated kinase in the hyperplastic response of Middle Ear Mucosa during bacterial otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Christoph Aletsee, Ayse G Kayali, Asa Melhus, Nicholas J G Webster, Allen F Ryan
    Abstract:

    Hyperplasia of Middle-Ear Mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the Middle Ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.

  • growth factors and their receptors in the Middle Ear Mucosa during otitis media
    2002
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Thecla Bennett, Allen F Ryan
    Abstract:

    Objective: The hyperplastic response of the Middle Ear Mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors. The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the Middle Ear Mucosa during otitis media. Study Design: Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat Middle Ear with bacteria. Methods: The Middle Ears of 12 male Sprague-Dawley rats were injected with 10 5 /mL Haemophilus influenzae strain 3655 (nontypeable, biotype II). Three rats were killed at 6, 24, 48, and 72 hours. Three untreated rats were also killed to serve as negative controls. The Middle Ear Mucosa samples were surgically removed and homogenized. Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor , hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-a. Results: Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal Middle Ear Mucosa. Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested. Betacellulin and neuregulin-a products were present at all time points except 72 hours after infection. Conclusions: The results of the study support a role for growth factors in the Middle Ear Mucosa during otitis media. These bioactive ingredients contribute to Mucosal hyperplasia.

  • growth factors influence growth and differentiation of the Middle Ear Mucosa
    2001
    Co-Authors: Sean D Palacios, Kwang Pak, Alexander Z Rivkin, Heinz Oehl, Christoph Aletsee, Allen F Ryan
    Abstract:

    Objective Otitis media is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by Mucosal hyperplasia that is thought to be mediated by the complex actions of growth factors and their respective receptors. It was the purpose of this study to determine which growth factors might be responsible for the growth and differentiation of the Middle Ear epithelium during otitis media. Study Design The effect of several growth factors on the expansion and differentiation of normal Middle Ear Mucosa was evaluated in tissue culture. Materials and Methods Explants of normal rat Middle Ear Mucosa were exposed in vitro to six different growth factors known to influence epithelial cells in other tissues: epidermal growth factor, amphiregulin, betacellulin, heregulin-α, keratinocyte growth factor, and hepatocyte growth factor. Results After 12 days, the growth and level of cytokeratin expression were analyzed for each of the explant outgrowths. Each factor appEared to have a significant, concentration-dependent effect on either the growth or differentiation of the cultured Middle Ear epithelial cells. Conclusion The results suggest that several of the tested growth factors may play a significant role in controlling hyperplasia of the Middle Ear Mucosa during otitis media.