PubMed Health⌕ Search

Biomedical subjects

A O'Mahony

Publications and source records attributed to A O'Mahony.

12 recordsLinked to original sources
PubMed2000

The NF-kappa B-inducing kinase induces PC12 cell differentiation and prevents apoptosis.

NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase activation and induced nuclear translocation of NF-kappa B. However, NIK-induced neurite outgrowth was only partially blocked by concomitant expression of a nondegradable form of I kappa B alpha that completely blocks NF-kappa B induction. In search of additional signaling pathways activated by NIK, we now demonstrate that NIK activates MEK1 phosphorylation and induces the Erk1/Erk2 MAPK pathway. Treatment of PC12 cells with PD98059, a MEK1 inhibitor, potently blocked neurite process formation; however, a dominantly interfering mutant of the upstream Shc adapter failed to alter this response. These findings reveal a new function for NIK as a MEK1-dependent activator of the MAPK pathway and implicate both the I kappa B kinase and MAPK signaling cascades in NIK-induced differentiation of PC12 cells.

Animals↗
PubMed2000

NF-kappa B signaling promotes both cell survival and neurite process formation in nerve growth factor-stimulated PC12 cells.

Nerve growth factor binds to the TrkA and p75(NTR) (p75) and generates signals leading to neuronal cell survival, differentiation, and programmed cell death. Here we describe a series of experiments involving selective activation of either TrkA or p75 in which distinct cell-signaling intermediates promote different cellular consequences. We analyzed pheochromocytoma 12 (PC12) cells stably expressing chimeras consisting of the extracellular domain of PDGF receptor (PDGFR) fused to the transmembrane and cytoplasmic segments of p75 or TrkA. Because PC12 cells lack endogenous PDGFR, addition of PDGF to these cell lines permits selective activation of the p75 or TrkA responses without stimulating endogenous receptors. Although both p75 and TrkA activated nuclear factor-kappaB (NF-kappaB), we show that distinct proximal-signaling intermediates are used by each receptor. A dominant-negative mutant of TRAF6 blocked p75- but not TrkA-mediated induction of NF-kappaB. Conversely a dominant-negative mutant of Shc inhibited TrkA but not p75 activation of NF-kappaB. Both of these distinct signaling pathways subsequently converge, leading to activation of the IkappaB kinase complex. Moreover, the activation of NF-kappaB by these distinct pathways after stimulation of either TrkA or p75 leads to different physiological consequences. Blocking p75-mediated activation of NF-kappaB by ecdysone-inducible expression of a nondegradable mutant of IkappaBalpha significantly enhanced apoptosis. In contrast, blocking NF-kappaB induction via TrkA significantly inhibited neurite process formation in PC12 cells. Together these findings indicate that, although both of these receptors lead to the activation of NF-kappaB, they proceed via distinct proximal-signaling intermediates and contribute to different cellular outcomes.

Animals↗
PubMed2000

Stress distribution in the single-unit osseointegrated dental implant: finite element analyses of axial and off-axial loading.

Occlusal overload may contribute to the extensive crestal bone loss often noted around late-failure dental implants. A particularly high risk of traumatic overload occurs with the posterior single-unit implant restoration because the restoration itself is usually wider than the implant, creating the potential for a cantilever effect with high bending moments. The objective of this study was to evaluate the simulated effects of axial and off-axial vertical loads on stress gradients at the implant/bone interface of a single-unit osseointegrated root-form endosseous dental implant. A two-dimensional finite element model was generated. A 490-N load was applied at 0, 2, 4, and 6 mm from the vertical axis of the implant. Off-axis loading resulted in greatly increased compressive stresses within the crestal cortical bone on the side to which the load was applied and similarly increased tensile stresses on the side opposite the load. These stresses increased considerably with each mm increase off axis of the applied load. These data suggest that off-axis loading of single-unit implant restorations provides a significant contribution to increased stresses at the implant/cortical bone interface. The distance off axis at which the load is applied is also significant.

Bite Force↗
PubMed2000

Activation of the heterodimeric IkappaB kinase alpha (IKKalpha)-IKKbeta complex is directional: IKKalpha regulates IKKbeta under both basal and stimulated conditions.

Signal-induced nuclear expression of the eukaryotic NF-kappaB transcription factor involves the stimulatory action of select mitogen-activated protein kinase kinase kinases on the IkappaB kinases (IKKalpha and IKKbeta) which reside in a macromolecular signaling complex termed the signalsome. While genetic studies indicate that IKKbeta is the principal kinase involved in proinflammatory cytokine-induced IkappaB phosphorylation, the function of the equivalently expressed IKKalpha is less clear. Here we demonstrate that assembly of IKKalpha with IKKbeta in the heterodimeric signalsome serves two important functions: (i) in unstimulated cells, IKKalpha inhibits the constitutive IkappaB kinase activity of IKKbeta; (ii) in activated cells, IKKalpha kinase activity is required for the induction of IKKbeta. The introduction of kinase-inactive IKKalpha, activation loop mutants of IKKalpha, or IKKalpha antisense RNA into 293 or HeLa cells blocks NIK (NF-kappaB-inducing kinase)-induced phosphorylation of the IKKbeta activation loop occurring in functional signalsomes. In contrast, catalytically inactive mutants of IKKbeta do not block NIK-mediated phosphorylation of IKKalpha in these macromolecular signaling complexes. This requirement for kinase-proficient IKKalpha to activate IKKbeta in heterodimeric IKK signalsomes is also observed with other NF-kappaB inducers, including tumor necrosis factor alpha, human T-cell leukemia virus type 1 Tax, Cot, and MEKK1. Conversely, the theta isoform of protein kinase C, which also induces NF-kappaB/Rel, directly targets IKKbeta for phosphorylation and activation, possibly acting through homodimeric IKKbeta complexes. Together, our findings indicate that activation of the heterodimeric IKK complex by a variety of different inducers proceeds in a directional manner and is dependent on the kinase activity of IKKalpha to activate IKKbeta.

Cell Line↗
PubMed2000

Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta.

The NF-kappaB/Rel family of eukaryotic transcription factors plays an essential role in the regulation of inflammatory, antiapoptotic, and immune responses. NF-kappaB is activated by many stimuli including costimulation of T cells with ligands specific for the T-cell receptor (TCR)-CD3 complex and CD28 receptors. However, the signaling intermediates that transduce these costimulatory signals from the TCR-CD3 and CD28 surface receptors leading to nuclear NF-kappaB expression are not well defined. We now show that protein kinase C-theta (PKC-theta), a novel PKC isoform, plays a central role in a signaling pathway induced by CD3-CD28 costimulation leading to activation of NF-kappaB in Jurkat T cells. We find that expression of a constitutively active mutant of PKC-theta potently induces NF-kappaB activation and stimulates the RE/AP composite enhancer from the interleukin-2 gene. Conversely, expression of a kinase-deficient mutant or antisense PKC-theta selectively inhibits CD3-CD28 costimulation, but not tumor necrosis factor alpha-induced activation of NF-kappaB in Jurkat T cells. The induction of NF-kappaB by PKC-theta is mediated through the activation of IkappaB kinase beta (IKKbeta) in the absence of detectable IKKalpha stimulation. PKC-theta acts directly or indirectly to stimulate phosphorylation of IKKbeta, leading to activation of this enzyme. Together, these results implicate PKC-theta in one pathway of CD3-CD28 costimulation leading to NF-kappaB activation that is apparently distinct from that involving Cot and NF-kappaB-inducing kinase (NIK). PKC-theta activation of NF-kappaB is mediated through the selective induction of IKKbeta, while the Cot- and NIK-dependent pathway involves induction of both IKKalpha and IKKbeta.

CD28 Antigens↗
PubMed2000

Effect of 3 medicaments on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions.

OBJECTIVE: The purpose of this study was to determine the effect of retraction cord medicaments (aluminum chloride, ferric sulfate, and ferric subsulfate/ferric sulfate) on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions. METHOD AND MATERIALS: Polyvinyl siloxane impressions were made of standardized metal dies (American Dental Association [ADA] specification No. 19) treated with 1 of the 3 retraction cord medicaments. Dimensional accuracy was evaluated by comparing the average length of a line in the impressions to the standard die. Surface detail reproduction was evaluated by viewing the impressions under low-angle illumination at x10 magnification. Reproduction was considered satisfactory if 2 of 3 horizontal lines were reproduced continuously. The dies were also evaluated under the microscope before the impression was made. RESULTS: The medicaments did not significantly effect the dimensional accuracy; mean shrinkage was within ADA guidelines in the treatment groups. All of the medicaments had an adverse effect on surface detail reproduction. These effects were statistically significant compared to the untreated control. CONCLUSION: Although the changes in dimensional accuracy were within ADA guidelines, the surface detail reproduction was modified such that the impression would be considered clinically unacceptable. For optimal results, care must taken to remove all traces of these retraction cord medicaments prior to recording of a polyvinyl siloxane impression.

Aluminum Chloride↗
PubMed2000

Design features that may influence bacterial plaque retention: a retrospective analysis of failed implants.

OBJECTIVE: The purpose of this study was to conduct a postmortem examination of retrieved failed dental implants to identify design characteristics that may have contributed to premature loss. METHOD AND MATERIALS: Forty-five failed implants retrieved from 40 patients with no significant risk factors for implant failure (e.g., history of smoking or diabetes) were examined by scanning electron microscopy. All implants were placed by general dentists or periodontists in private practice and had functioned for an average of 4 years. RESULTS: Several design features of currently used implants present plaque-retentive areas. Plaque accumulation occurred along the implant-transmucosal abutment interfaces, transmucosal abutment-prosthesis interfaces, implant-prosthesis interfaces, and on surfaces of the abutment, the implant, and the prosthesis. The size of the microgap between the various components, the degree of surface roughness of the restorations and abutments, the exposure of plasma-sprayed coatings and threaded surfaces of implants, and overcontouring of implant restorations contributed to plaque accumulation and provided an ideal environment for bacterial colonization. CONCLUSION: These implant features may be key precipitating or exacerbating factors in the development of peri-implant inflammation, predisposing patients to implant failure.

Adult↗
PubMed2000

Dentin bonding agents and resin cements--current status.

Contemporary restorative dentistry is a rapidly evolving science which challenges the progressive clinician with a plethora of "new and improved" products. Sound product choices should be couched in the prudent consideration of well conducted in vitro and in vivo product research. This review shall list the most recent product developments in dentin bonding agents (fifth generation agents), resin-containing dental cements and the newest generation of dental cements i.e., resin-ionomer dental cements.

Acid Etching, Dental↗
PubMed1999

Osseointegrated implant failures.

This article discusses the criteria used for implant success and failure, the classification of implant failures, the causative factors, and diagnosis of the failing and failed implant. In spite of the impressive success rates of osseointegrated dental implants, failures occur and in some studies the incidence of failure is high. Many studies do not use objective criteria to define success and confuse survival with success. The criteria used affect reported success rates. Implant failures may occur early (primary) after implant placement or after the implant is loaded (secondary). There is no single aetiological factor and failures have been attributed to poor surgical technique, host factors that impair healing, poor bone quality, peri-implant infections, poor prosthesis design and traumatic loading conditions. Early diagnosis of problems is critical and every effort should be made to treat the problem while the damage can still be managed or even reversed.

Biomechanical Phenomena↗
PubMed1999

Restoration of endodontically treated teeth with posts and cores.

This article is a review of the current technique and materials used in the restoration of endodontically treated teeth with post and core materials and procedures. It is intended to aid clinicians in making selections which are appropriate to their individual practices through the evaluation of relevant literature about the restoration of endodontically treated teeth.

Dental Prosthesis Design↗
PubMed1998

Loss of crestal bone around dental implants: a retrospective study.

The loss of crestal bone associated with dental implants is a significant clinical phenomenon. The occurrence of such bone loss will often compromise long-term prognosis and, if extensive, ultimately lead to failure. Relatively few studies have focused on the reasons for loss of crestal-supporting bone around implants, although numerous explanations for the phenomenon have been proposed. This retrospective investigation examines one potential causative factor for implant-associated crestal bone loss, which has only recently received attention, i.e., location of the implant/transmucosal abutment interface (ITAI) relative to the crestal bone. A retrospective clinical evaluation of 350 individual implants in 255 patients indicates a direct relationship between subgingival placement of the ITAI and loss of crestal supporting bone. In addition, scanning electron microscopic examination of 45 failed implants showed significant plaque accumulation at the ITAI, the transmucosal abutment/prosthesis interface (TAPI), and the interface between the implant smooth collar and subjacent plasma-spray coated surface.

Adolescent↗