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1.
Radiography (Lond) ; 30(2): 628-633, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330895

RESUMO

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Estudos Retrospectivos , Neoplasias Testiculares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste
2.
Hernia ; 28(2): 301-319, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37715026

RESUMO

PURPOSE: Incisional hernia (IH) post renal transplant (RT) is relatively uncommon and can be challenging to manage clinically due to the presence of the kidney graft and patient immunosuppression. This systematic review and meta-analysis synthesises the current literature in relation to IH rates, risk factors and outcomes post RT. METHODS: PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched up to July 2023. The most up to date Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were followed. Pertinent clinical information was synthesised. A meta-analysis of the pooled proportions of IH rates, the rates of patients requiring surgical repair and the rates of recurrence post RT are reported. RESULTS: Twenty studies comprising 16,018 patients were included in this analysis. The pooled rate of IH occurrence post RT was 4% (CI 3-5%). The pooled rate of IH repair post RT was 61% (CI 14-100%). The pooled rate of IH recurrence after repair was 16% (CI 9-23%). Risk factors identified for IH development post RT are BMI, immunosuppression, age, smoking, incision type, reoperation, concurrent abdominal wall hernia, lymphocele formation and pulmonary disease. CONCLUSIONS: IH post RT is uncommon and the majority of IH post RT are repaired surgically on an elective basis.


Assuntos
Hérnia Ventral , Hérnia Incisional , Transplante de Rim , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Transplante de Rim/efeitos adversos , Herniorrafia/efeitos adversos , Hérnia Ventral/complicações , Rim
3.
Radiography (Lond) ; 29(4): 712-720, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37196480

RESUMO

BACKGROUND: Cross-sectional study to assess the body composition of patients with Crohn's disease (CD) on standard (SDCT) and low dose CT (LDCT) protocols for the abdomen and pelvis (CTAP). We aimed to assess if a low dose CT protocol reconstructed with model-based iterative reconstruction (IR) could evaluate body morphometric data comparable to standard dose examination. METHODS: The CTAP images of 49 patients who underwent a low dose CT scan (20% of standard dose) and a second at standard dose minus 20% were assessed retrospectively. Images were collected from the PACS system, deidentified and analysed using a web-based semi-automated threshold-based segmentation tool (CoreSlicer), capable of identifying tissue type based on differences in attenuation co-efficient. The cross-sectional area (CSA) and Hounsfield units (HU) of each tissue was recorded. RESULTS: Muscle and fat CSA is well preserved on comparing these derived metrics from low dose and standard dose CT scans of abdomen and pelvic in CD ((LDCT:SDCT mean CSA (cm2); Psoas muscle - 29.00:28.67, total lumbar muscle - 127.45:125.55, visceral fat- 110.44:114.16, subcutaneous fat - 250.88:255.05)). A fixed difference exists when assessing the attenuation of muscle, with higher attenuation on the low dose protocol (LDCT:SDCT mean attenuation (HU); Psoas muscle - 61.67:52.25, total lumbar muscle - 49.29:41.20). CONCLUSION: We found comparable CSA across all tissues (muscle and fat) on both protocols with a strong positive correlation. A marginally lower muscle attenuation suggestive of less dense muscle was highlighted on SDCT. This study augments previous studies suggesting that comparable and reliable morphomic data may be generated from low dose and standard dose CT images. IMPLICATIONS FOR PRACTICE: Threshold-based segmental tools can be used to quantify body morphomics on standard and low dose computed tomogram protocols.


Assuntos
Doença de Crohn , Humanos , Doses de Radiação , Doença de Crohn/diagnóstico por imagem , Estudos Retrospectivos , Estudos Transversais , Tomografia Computadorizada por Raios X/métodos
4.
Radiography (Lond) ; 28(4): 943-948, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35839662

RESUMO

INTRODUCTION: Artificial intelligence (AI) is increasingly utilised in medical imaging systems and processes, and radiographers must embrace this advancement. This study aimed to investigate perceptions, knowledge, and expectations towards integrating AI into medical imaging amongst a sample of radiographers and determine the current state of AI education within the community. METHODS: A cross-sectional online quantitative study targeting radiographers based in Europe was conducted over ten weeks. Captured data included demographical information, participants' perceptions and understanding of AI, expectations of AI and AI-related educational backgrounds. Both descriptive and inferential statistical techniques were used to analyse the obtained data. RESULTS: A total of 96 valid responses were collected. Of these, 64% correctly identified the true definition of AI from a range of options, but fewer (37%) fully understood the difference between AI, machine learning and deep learning. The majority of participants (83%) agreed they were excited about the advancement of AI, though a level of apprehensiveness remained amongst 29%. A severe lack of education on AI was noted, with only 8% of participants having received AI teachings in their pre-registration qualification. CONCLUSION: Overall positive attitudes towards AI implementation were observed. The slight apprehension may stem from the lack of technical understanding of AI technologies and AI training within the community. Greater educational programs focusing on AI principles are required to help increase European radiography workforce engagement and involvement in AI technologies. IMPLICATIONS FOR PRACTICE: This study offers insight into the current perspectives of European based radiographers on AI in radiography to help facilitate the embracement of AI technology and convey the need for AI-focused education within the profession.


Assuntos
Inteligência Artificial , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Humanos , Motivação , Radiografia
6.
Ir Med J ; 112(9): 1007, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31651136

RESUMO

Presentation A 37-year-old Polish male presented with headache, myalgia, rash and reduced visual acuity. Diagnosis Measles was confirmed on day 5 via throat swab, complicated by ocular keratitis which was diagnosed by slit lamp exam using fluorescein staining. Treatment Once the diagnosis was confirmed, the patient received supportive medical treatment and topical treatment with six - hourly preservative free dexamethasone and sodium hyaluronate to both eyes was prescribed. Conclusion Measles cases have increased by 244% in Ireland1 remaining an important public health concern. This case illustrates the difficulty in diagnosis, ocular manifestations and serves to remind health care professionals that this potentially devastating disease has not gone away.


Assuntos
Ceratite/tratamento farmacológico , Ceratite/etiologia , Sarampo/induzido quimicamente , Adulto , Dexametasona/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Masculino
8.
Br Dent J ; 222(9): 677-681, 2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28496230

RESUMO

Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it exhibits very aggressive behaviour compared with typical external root resorption, posing a high risk of tooth loss.Aim To investigate the number of patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft who experienced ICR and to identify any possible aetiological factors.Materials and method A retrospective investigation of all oro-facial cleft patients treated at the Dublin Cleft Prosthodontic Department, St James's Hospital, Dublin. All patients' clinical and radiological records were reviewed. Patients where tooth loss became inevitable due to Class 4 ICR were analysed.Results From 588 oro-facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28 years (range = 16-49 years). Cleft type: six (42.1%) unilateral cleft lip and palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though not immediate, was inevitable. All had undergone fixed orthodontic appliance treatment and twelve had received dento-alveolar bone grafts. A number (N = 7, 50%) had undergone osteotomy, two (14%) had received night guard vital dental whitening and one had a history of trauma.Conclusions ICR, given its aggressive nature and ill-understood aetiology, poses significant treatment challenges. The most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow-moderate progression of ICR may explain the late presentation found in this study, reinforcing the importance of long-term follow-up of this special dental care group.


Assuntos
Fenda Labial/complicações , Fissura Palatina/complicações , Reabsorção da Raiz/etiologia , Adolescente , Adulto , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Pré-Protéticos Bucais/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Reabsorção da Raiz/epidemiologia , Adulto Jovem
9.
J Aerosol Med Pulm Drug Deliv ; 27(6): 466-77, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24665866

RESUMO

BACKGROUND: Successful delivery of small interfering RNA (siRNA) to the lungs remains hampered by poor intracellular delivery, vector-mediated cytotoxicity, and an inability to withstand nebulization. Recently, a novel cyclodextrin (CD), SC12CDClickpropylamine, consisting of distinct lipophilic and cationic subunits, has been shown to transfect a number of cell types. However, the suitability of this vector for pulmonary siRNA delivery has not been assessed to date. To address this, a series of high-content analysis (HCA) and postnebulization assays were devised to determine the potential for CD-siRNA delivery to the lungs. METHODS: SC12CDClickpropylamine-siRNA mass ratios (MRs) were examined for size and zeta potential. In-depth analysis of nanocomplex uptake and toxicity in Calu-3 bronchial epithelial cells was examined using IN Cell(®) HCA assays. Nebulized SC12CDClickpropylamine nanocomplexes were assessed for volumetric median diameter (VMD) and fine particle fraction (FPF) and compared with saline controls. Finally, postnebulization stability was determined by comparing luciferase knockdown elicited by SC12CDClickpropylamine nanocomplexes before and after nebulization. RESULTS: SC12CDClickpropylamine-siRNA complexation formed cationic nanocomplexes of ≤200 nm in size depending on the medium and led to significantly higher levels of siRNA associated with Calu-3 cells compared with RNAiFect-siRNA-treated cells at all MRs (p<0.001, n=3×4), with evidence of toxicity only at MRs 50-100. Nebulization of SC12CDClickpropylamine nanocomplexes using the Aeroneb(®) Pro resulted in VMDs of ∼4 µm and FPFs of ∼57% at all MRs. SC12CDClickpropylamine-siRNA-mediated luciferase knockdown was found to be 39.8±3.6% at MR=20 before and 35.6±4.55% after nebulization, comparable to results observed using unnebulized commercial transfection reagent, RNAiFect. CONCLUSIONS: SC12CDClickpropylamine nanocomplexes can be effectively nebulized for pulmonary delivery of siRNA using Aeroneb technology to mediate knockdown in airway cells. To the best of our knowledge, this is the first study examining the suitability of SC12CDClickpropylamine-siRNA nanocomplexes for pulmonary delivery. Furthermore, this work provides an integrated nanomedicine-device combination for future in vitro and in vivo preclinical and clinical studies of inhaled siRNA therapeutics.


Assuntos
Nanopartículas , Nebulizadores e Vaporizadores , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Transfecção/métodos , beta-Ciclodextrinas/administração & dosagem , Administração por Inalação , Linhagem Celular , Regulação da Expressão Gênica , Genes Reporter , Ensaios de Triagem em Larga Escala , Humanos , Luciferases/genética , Luciferases/metabolismo , Tamanho da Partícula , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Tempo , beta-Ciclodextrinas/química , beta-Ciclodextrinas/toxicidade
10.
Eur J Pharm Sci ; 47(5): 896-903, 2012 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-23022516

RESUMO

Significant research is focused on the development of non-viral vectors for delivery of siRNA to neurons and the central nervous system. Cyclodextrins (CDs) have shown great promise as efficient and low toxicity gene delivery vectors in various cell types. Here, we investigate two CDs for siRNA delivery in a neuronal cell model. These CDs were substituted on opposite faces (primary and secondary) with amphiphilic and cationic groups. Physical properties of CD.siRNA complexes, including size, charge and stability were measured. In vitro investigations were carried out in immortalised hypothalamic neurons. Neuronal cell uptake was measured by flow cytometry and cytotoxicity was assessed by MTT assay. Knockdown of a luciferase reporter gene was used as a measure of gene silencing efficiency. Both CDs interacted with siRNA, yielding nanosized cationic complexes which exhibited good stability on storage. A favourable toxicity profile was demonstrated for the CD.siRNA complexes. However, only one of the two CDs mediated high levels of neuronal uptake and efficient gene silencing, equivalent to those achieved with a commercial lipid-based vector. Despite the suitability of both CDs as siRNA delivery vectors in terms of their ability to complex siRNA and the properties of the complexes yielded, only one CD achieved good transfection efficiency. This was likely due to the differences in their chemical structures. The effective CD offers great potential as a novel non-toxic vector for neuronal siRNA delivery.


Assuntos
Ciclodextrinas/administração & dosagem , Neurônios/metabolismo , RNA Interferente Pequeno/administração & dosagem , Transfecção/métodos , Animais , Linhagem Celular , Ciclodextrinas/química , Inativação Gênica , Genes Reporter/genética , Luciferases de Vaga-Lume/genética , Luciferases de Vaga-Lume/metabolismo , Camundongos , RNA Interferente Pequeno/química , Relação Estrutura-Atividade
11.
ACS Chem Neurosci ; 3(10): 744-52, 2012 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-23077718

RESUMO

RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date, they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified ß-cyclodextrin (CD) vector was synthesized, which complexed siRNA to form cationic nanoparticles of less than 200 nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalized hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labeled siRNA, while maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.


Assuntos
Química Click/métodos , Ciclodextrinas/química , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Neurônios/metabolismo , RNA Interferente Pequeno/genética , Animais , Células Cultivadas , Ciclodextrinas/administração & dosagem , Vetores Genéticos/administração & dosagem , Vetores Genéticos/metabolismo , Neurônios/efeitos dos fármacos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley
12.
Chem Asian J ; 5(2): 202-30, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20013990

RESUMO

The recent literature is surveyed to explore the nature of voltammetry in room temperature ionic liquids. The extent of similarities with conventional electrochemical solvents is reported and some surprising differences are noted.


Assuntos
Técnicas Eletroquímicas , Líquidos Iônicos/química , Temperatura , Eletroquímica , Solventes/química
13.
J Oral Rehabil ; 30(6): 573-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12787453

RESUMO

To test the hypothesis that a flat plane interocclusal appliance affects the electromyographic (EMG) activity of the temporalis and masseter muscles in pain-free individuals, maxillary splints were fabricated for 20 individuals who reported no history, signs or symptoms of myofascial pain or arthralgia as determined by two trained, independent examiners. Subjects were instructed to establish light tooth contact, maximum clenching, and moderate clenching with/without the splint in place (as determined by random assignment) while EMG data from the left and right temporalis and masseter muscles were recorded. A 5-min biofeedback training session to relax the masticatory muscles was followed by a repetition of the tooth contact/clenching tasks with/without the splint in place. With the splint in place, the activity of the temporalis muscles decreased for all tasks, significantly for the left and right temporalis under maximal clenching and for the right temporalis under moderate clenching. In contrast, the activity of the masseter muscles increased under light and moderate clenching (significantly for the left masseter under moderate clenching) and decreased slightly under maximal clenching. The effectiveness of interocclusal appliances may be due to mechanisms other than redistribution of adverse loading.


Assuntos
Bruxismo , Eletromiografia , Músculo Masseter/fisiologia , Placas Oclusais , Músculo Temporal/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Bruxismo/fisiopatologia , Humanos , Placas Oclusais/normas
14.
Clin Oral Implants Res ; 12(6): 648-57, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11737110

RESUMO

The aim of this study was to compare implant-bone interface stresses and peri-implant principal strains in anisotropic versus isotropic three-dimensional finite element models of an osseointegrated implant in the posterior mandible. We obtained anisotropic (transversely isotropic) elastic constants for mandibular bone and derived equivalent isotropic constants by averaging over all possible spatial orientations. A finite element model was constructed using ten-node tetrahedral p-elements, providing curved edges where necessary and increasing the accuracy of the results in regions of high stress gradients. Perfect bonding was assumed at the implant-bone interface. An oblique load was applied at the coronal aspect of the crown with 100 N vertical and 20 N bucco-to-lingual components. Implant-bone interface stresses exceeded reported bond strengths and principal strains reached yield strain levels in the cortical crest. Anisotropy increased what were already high levels of stress and strain in the isotropic case by 20 to 30% in the cortical crest. In cancellous bone, anisotropy increased what were relatively low levels of interface stress in the isotropic case by three- to four-fold to exceed bond strength levels. Anisotropy has subtle, yet significant effects on interface stresses and peri-implant strains and careful consideration should be given to its use in finite element studies of dental implants.


Assuntos
Processo Alveolar/fisiologia , Implantes Dentários para Um Único Dente , Análise do Estresse Dentário , Anisotropia , Força Compressiva , Elasticidade , Análise de Elementos Finitos , Humanos , Mandíbula/fisiologia , Modelos Biológicos , Estresse Mecânico , Resistência à Tração
15.
J Neurosci ; 20(20): 7556-63, 2000 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11027214

RESUMO

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.


Assuntos
Proteínas I-kappa B , NF-kappa B/metabolismo , Fator de Crescimento Neural/metabolismo , Neuritos/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/genética , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Genes Dominantes , Inibidor de NF-kappaB alfa , NF-kappa B/farmacologia , Fator de Crescimento Neural/farmacologia , Neuritos/efeitos dos fármacos , Neuritos/ultraestrutura , Células PC12/efeitos dos fármacos , Células PC12/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Ratos , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
16.
J Biol Chem ; 275(44): 34021-4, 2000 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-10980190

RESUMO

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.


Assuntos
Apoptose/fisiologia , Diferenciação Celular/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Sequência de Bases , Oligonucleotídeos , Células PC12 , Fosforilação , Ratos , Transdução de Sinais , Quinase Induzida por NF-kappaB
17.
Mol Cell Biol ; 20(8): 2933-40, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10733597

RESUMO

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.


Assuntos
Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Isoenzimas/metabolismo , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Humanos , Quinase I-kappa B , Isoenzimas/genética , Células Jurkat , Mutação , Proteína Quinase C/genética , Proteína Quinase C-theta , Transdução de Sinais
18.
Mol Cell Biol ; 20(4): 1170-8, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10648602

RESUMO

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.


Assuntos
MAP Quinase Quinase Quinase 1 , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Linhagem Celular , Dimerização , Ativação Enzimática , Produtos do Gene tax/farmacologia , Células HeLa , Humanos , Quinase I-kappa B , MAP Quinase Quinase Quinases/metabolismo , Mutação , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Estrutura Quaternária de Proteína , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologia
19.
Clin Oral Implants Res ; 11(5): 415-21, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11168233

RESUMO

The elastic moduli have not been reported for cancellous bone from the edentulous mandible. Accurate values are needed for finite element modeling of the mandible. The aim of this study was to determine elastic modulus values in three orthogonal directions for cancellous bone taken from an edentulous jaw and to relate these values to apparent density and volume fraction. Seven samples were obtained from the edentulous mandible of a 74-year-old female. Young's modulus was determined by compression testing of cubes cut with the faces aligned with the anatomic axes. Bone volume fraction averaged 0.33 (SD 0.14) and apparent density averaged 0.55 g/cc (SD 0.29). Young's modulus was greatest in the mesio-distal direction (mean 907 MPa, SD 849 MPa), followed by the bucco-lingual (mean 511 MPa, SD 565 MPa) and infero-superior direction (mean 114 MPa, SD 78 MPa). The infero-superior direction was less than the bucco-lingual (P = 0.03) and mesio-distal (P = 0.002). The mesio-distal and bucco-lingual directions could not be shown to be different (P = 0.32). This suggests a model of transverse isotropy for cancellous bone in the jaw, where the symmetry axis is along the infero-superior (weakest) direction.


Assuntos
Arcada Edêntula/fisiopatologia , Mandíbula/fisiopatologia , Idoso , Perda do Osso Alveolar/fisiopatologia , Análise de Variância , Anisotropia , Densidade Óssea , Força Compressiva , Elasticidade , Feminino , Humanos , Modelos Lineares , Manejo de Espécimes , Estatísticas não Paramétricas
20.
J Ir Dent Assoc ; 46(2): 44-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11326526

RESUMO

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.


Assuntos
Adesivos Dentinários/química , Cimentos de Resina/química , Condicionamento Ácido do Dente/métodos , Compômeros/química , Compômeros/classificação , Colagem Dentária/métodos , Adesivos Dentinários/classificação , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/classificação , Humanos , Cimentos de Resina/classificação , Fatores de Tempo
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