Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Oral Rehabil ; 51(5): 785-794, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151896

RESUMO

BACKGROUND: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings. OBJECTIVE: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management. METHODS: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields. The process comprised a full day workshop, seven virtual meetings, six rounds of electronic discussion and finally an open consultation at a virtual international symposium. RESULTS: Within the physical axis (Axis 1), the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to four sections in the bDC/TMD protocol involving three movements and three sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The psychosocial axis (Axis 2) was shortened to an ultra-brief 11 item assessment. CONCLUSION: The bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.


Assuntos
Dor Facial , Transtornos da Articulação Temporomandibular , Humanos , Dor Facial/diagnóstico , Cefaleia/diagnóstico , Exame Físico , Palpação
2.
J Craniofac Surg ; 25(6): e548-55, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25364968

RESUMO

PURPOSE: Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes that are down-regulated in patients with facial asymmetry. METHODS: Masseter muscle samples were collected during bilateral sagittal split osteotomy orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. RESULTS: Overall gene expression was different for asymmetric patients compared with other malocclusion classifications by principal component analysis (P < 0.05). We identified differences in the nodal signaling pathway, which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39- to 1.84-fold greater (P < 3.41 × 10), whereas integral membrane Nodal modulators Nomo1,2,3 were -5.63 to -5.81 (P < 3.05 × 10) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of -7.02 to -2.47 (P < 0.003). Finally Pitx2, an upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P < 0.05). CONCLUSIONS: When facial asymmetry is part of skeletal malocclusion, there are decreases in nodal signaling pathway genes in masseter muscle. This data suggest that the nodal signaling pathway is down-regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition.


Assuntos
Regulação para Baixo/genética , Assimetria Facial/genética , Proteína Nodal/genética , Transdução de Sinais/genética , Adulto , Assimetria Facial/patologia , Feminino , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fatores de Determinação Direita-Esquerda/genética , Masculino , Má Oclusão/genética , Má Oclusão/patologia , Músculo Masseter/metabolismo , Músculo Masseter/patologia , Proteínas de Membrana/genética , Fatores de Transcrição/genética , Proteína Homeobox PITX2
3.
Am J Orthod Dentofacial Orthop ; 146(5): 603-11, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25439211

RESUMO

INTRODUCTION: α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. METHODS: Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. RESULTS: Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P <0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P = 0.002). CONCLUSION: ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.


Assuntos
Actinina/genética , Arginina/genética , Má Oclusão Classe II de Angle/genética , Sobremordida/genética , Polimorfismo Genético/genética , Biópsia , Códon de Terminação/genética , Citosina , Éxons/genética , Feminino , Frequência do Gene/genética , Variação Genética/genética , Genótipo , Humanos , Íntrons/genética , Masculino , Músculo Masseter/metabolismo , Músculo Masseter/patologia , Fibras Musculares de Contração Rápida/ultraestrutura , Fibras Musculares Esqueléticas/classificação , Fibras Musculares Esqueléticas/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Saliva/química , Timina , Adulto Jovem
4.
Chemphyschem ; 14(10): 2143-8, 2013 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-23703945

RESUMO

We describe an electrochemistry-based technique to control and monitor the polymerisation of sickle-cell haemoglobin (HbS). The polymerisation was monitored as a change in turbidity during the depletion of oxygen in a small volume custom-built thin-layer electrochemical cell. The cell allowed the investigation of HbS polymerisation as a function of HbS concentration, temperature and solution pH. We confirm that the oxygen was efficiently depleted using finite-element modelling to accurately recreate the electrochemical thin-layer cell. Understanding the nucleation and growth of HbS polymerisation will provide a better understanding of the pathophysiology of sickle-cell disease in vivo, and thus help improve therapeutic strategies for this common and frequently disabling disorder.


Assuntos
Anemia Falciforme/metabolismo , Técnicas Eletroquímicas , Hemoglobina Falciforme/biossíntese , Hemoglobina Falciforme/química , Hemoglobina Falciforme/metabolismo , Concentração de Íons de Hidrogênio , Oxigênio/química , Oxigênio/metabolismo , Polimerização , Temperatura
5.
Am J Orthod Dentofacial Orthop ; 144(4): 568-76, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24075665

RESUMO

INTRODUCTION: Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions. METHODS: Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction. RESULTS: Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX. CONCLUSIONS: These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.


Assuntos
Epigenômica , Histona Acetiltransferases/genética , Histona Desacetilases/genética , Músculo Masseter/efeitos dos fármacos , Mordida Aberta/genética , Sobremordida/genética , Proteínas Repressoras/genética , Feminino , Histona Acetiltransferases/farmacologia , Histona Desacetilases/farmacologia , Humanos , Masculino , Má Oclusão Classe II de Angle/genética , Má Oclusão Classe III de Angle/genética , Miosinas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras/farmacologia , Adulto Jovem
6.
J Oral Maxillofac Surg ; 70(2): 440-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21821327

RESUMO

PURPOSE: We identified masseter muscle fiber type property differences in subjects with dentofacial deformities. PATIENTS AND METHODS: Samples of masseter muscle were collected from 139 young adults during mandibular osteotomy procedures to assess mean fiber areas and percent tissue occupancies for the 4 fiber types that comprise the muscle. Subjects were classified into 1 of 6 malocclusion groups based on the presence of a skeletal Class II or III sagittal dimension malocclusion and either a skeletal open, deep, or normal bite vertical dimension malocclusion. In a subpopulation, relative quantities of the muscle growth factors IGF-I and GDF-8 gene expression were quantified by real-time polymerase chain reaction. RESULTS: Fiber properties were not different in the sagittal malocclusion groups, but were very different in the vertical malocclusion groups (P ≤ .0004). There were significant mean fiber area differences for type II (P ≤ .0004) and type neonatal-atrial (P = .001) fiber types and for fiber percent occupancy differences for both type I-II hybrid fibers and type II fibers (P ≤ .0004). Growth factor expression differed by gender for IGF-I (P = .02) and GDF-8 (P < .01). The ratio of IGF-I:GDF-8 expression associates with type I and II mean fiber areas. CONCLUSION: Fiber type properties are very closely associated with variations in vertical growth of the face, with statistical significance for overall comparisons at P ≤ .0004. An increase in masseter muscle type II fiber mean fiber areas and percent tissue occupancies is inversely related to increases in vertical facial dimension.


Assuntos
Fator de Crescimento Insulin-Like I/análise , Má Oclusão Classe III de Angle/patologia , Má Oclusão Classe II de Angle/patologia , Músculo Masseter/ultraestrutura , Fibras Musculares Esqueléticas/ultraestrutura , Miostatina/análise , Adolescente , Adulto , Miosinas Cardíacas/análise , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Desenvolvimento Maxilofacial/fisiologia , Fibras Musculares de Contração Rápida/ultraestrutura , Fibras Musculares de Contração Lenta/ultraestrutura , Miosina Tipo I/análise , Miosina Tipo II/análise , Miostatina/genética , Mordida Aberta/patologia , Sobremordida/patologia , Reação em Cadeia da Polimerase , RNA/análise , Fatores Sexuais , Dimensão Vertical , Adulto Jovem
7.
Proc Natl Acad Sci U S A ; 106(36): 15297-301, 2009 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-19706395

RESUMO

Coherent X-ray diffraction has been applied in the imaging of inorganic materials with great success. However, its application to biological specimens has been limited to some notable exceptions, due to the induced radiation damage and the extended nature of biological samples, the last limiting the application of most part of the phasing algorithms. X-ray ptychography, still under development, is a good candidate to overcome such difficulties and become a powerful imaging method for biology. We describe herein the feasibility of applying ptychography to the imaging of biological specimens, in particular collagen rich samples. We report here speckles in diffraction patterns from soft animal tissue, obtained with an optimized small angle X-ray setup that exploits the natural coherence of the beam. By phasing these patterns, dark field images of collagen within tendon, skin, bone, or cornea will eventually be obtained with a resolution of 60-70 nm. We present simulations of the contrast mechanism in collagen based on atomic force microscope images of the samples. Simulations confirmed the 'speckled' nature of the obtained diffraction patterns. Once inverted, the patterns will show the disposition and orientation of the fibers within the tissue, by enhancing the phase contrast between protein and no protein regions of the sample. Our work affords the application of the most innovative coherent X-ray diffraction tools to the study of biological specimens, and this approach will have a significant impact in biology and medicine because it overcomes many of the limits of current microscopy techniques.


Assuntos
Colágeno/ultraestrutura , Difração de Raios X/métodos , Microscopia de Força Atômica , Síncrotrons
8.
Cell Motil Cytoskeleton ; 66(7): 409-22, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19492400

RESUMO

Dynamic mechanical properties of cells are becoming recognized as indicators and regulators of physiological processes such as differentiation, malignant phenotypes and mitosis. A key process in development and homeostasis is apoptosis and whilst the molecular control over this pathway is well studied, little is known about the mechanical consequences of cell death. Here, we study the caspase-dependent mechanical kinetics of single cells during early apoptosis initiated with the general protein-kinase inhibitor staurosporine. This results in internal remodelling of the cytoskeleton and nucleus which is reflected in dynamic changes in the mechanical properties of the cell. Utilizing simultaneous confocal and atomic force microscopy (AFM), we measured distinct mechanical dynamics in the instantaneous cellular Young's Modulus and longer timescale viscous deformation. This allowed us to visualize time-dependent nuclear and cytoskeletal control of force dissipation with fluorescent fusion proteins throughout the cell. This work reveals that the cell death program not only orchestrates biochemical dynamics but also controls the mechanical breakdown of the cell. Importantly, the consequences of mechanical disregulation during apoptosis may be a contributing factor to several human pathologies through the poorly timed release of dead cells and cell debris.


Assuntos
Apoptose/fisiologia , Núcleo Celular/fisiologia , Citoesqueleto/fisiologia , Fibroblastos/fisiologia , Estresse Mecânico , Actinas/efeitos dos fármacos , Actinas/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Citocalasina D/farmacologia , Citoesqueleto/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Lamina Tipo A/efeitos dos fármacos , Lamina Tipo A/metabolismo , Microscopia de Força Atômica , Microscopia Confocal , Nocodazol/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Estaurosporina/farmacologia , Transfecção , Tubulina (Proteína)/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia
9.
Nanotechnology ; 20(28): 285103, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19546491

RESUMO

Retinol and conjugated linoleic acid (CLA) have previously been shown to have an important role in gene expression and various cellular processes, including differentiation, proliferation and cell death. In this study we have investigated the effect of retinol and CLA, both individually and in combination, on the intracellular cytoskeleton, focal adhesions (FAs) and the nanomechanical properties of 3T3 fibroblasts. We observed a dose-dependent decrease in the formation of FAs following treatment with either compound, which was directly correlated to an increase in cell height (>30%) and a decrease in the measured Young's modulus (approximately 28%). Furthermore, treatments with both compounds demonstrated an increased effect and led to a reduction of >70% in the average number of FAs per cell and a decrease of >50% in average cell stiffness. These data reveal that retinol and CLA disrupt FA formation, leading to an increase in cell height and a significant decrease in stiffness. These results may broaden our understanding of the interplay between cell nanomechanics and cellular contact with the external microenvironment, and help to shed light on the important role of retinoids and CLA in health and disease.


Assuntos
Fenômenos Biomecânicos/efeitos dos fármacos , Adesões Focais/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , Vitamina A/farmacologia , Vitaminas/farmacologia , Células 3T3 , Animais , Forma Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Relação Dose-Resposta a Droga , Camundongos , Microscopia de Força Atômica , Microscopia Confocal
10.
Prim Dent J ; 8(2): 30-33, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31431203

RESUMO

The term "human factors" has been batted around in the healthcare setting, and more recently in relation to dentistry. you may think this doesn't relate to you, but in reality, human factors encompass every member of the team in every process and procedure we carry out.
It is by recognising that human factors exist that we also recognise that as professionals we cannot be perfect all the time. recognising and attempting to mitigate those errors forms a fundamental part of human factors.
In our everyday life we make numerous errors which have little consequence normally, but they are all the result of human factors. if we translate the causes of these to healthcare, then to be distracted, to change routine or not make a list, for example, has consequences that may be much more serious.


Assuntos
Odontologia , Ergonomia , Humanos
11.
Surg Neurol Int ; 10: 101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528439

RESUMO

BACKGROUND: Intraoperative magnetic resonance imaging (ioMRI) has led to significant advancements in neurosurgery with improved accuracy, assessment of the extent of resection, less invasive surgical alternatives, and real-time confirmation of targeting as well delivery of therapies. The costs associated with developing ioMRI units in the surgical suite have been obstacles to the expansion of their use. More recently, the development of hybrid interventional MRI (iMRI) units has become a viable alternative. The process of designing, developing, and implementing operations for these units requires the careful integration of environmental, technical, and safety elements of both surgical and MR practices. There is a paucity of published literature providing guidance for institutions looking to develop a hybrid iMRI unit, especially with a limited footprint in the radiology department. METHODS: The experience of designing, developing, and implementing an iMRI in a preexisting space for neurosurgical procedures at a single institution in light of available options and the literature is described. RESULTS: The development of the unit was accomplished through the engagement of a multidisciplinary team of stakeholders who utilized existing guidelines and recommendations and their own professional experience to address issues including physical layout, equipment selection, operations planning, infection control, and oversight/review, among others. CONCLUSION: Successful creation of an iMRI program requires multidisciplinary collaboration in integrating surgical and MR practice. The authors' aim is that the experience described in this article will serve as an example for facilities or neurosurgical departments looking to navigate the same process.

12.
Biomaterials ; 29(11): 1553-62, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18164758

RESUMO

We describe experiments designed to explore the possibility of using amyloid fibrils as new nanoscale biomaterials for promoting and exploiting cell adhesion, migration and differentiation in vitro. We created peptides that add the biological cell adhesion sequence (RGD) or a control sequence (RAD) to the C-terminus of an 11-residue peptide corresponding to residues 105-115 of the amyloidogenic protein transthyretin. These peptides readily self-assemble in aqueous solution to form amyloid fibrils, and X-ray fibre diffraction shows that they possess the same strand and sheet spacing in the characteristic cross-beta structure as do fibrils formed by the parent peptide. We report that the fibrils containing the RGD sequence are bioactive and that these fibrils interact specifically with cells via the RGD group displayed on the fibril surface. As the design of such functionalized fibrils can be systematically altered, these findings suggest that it will be possible to generate nanomaterials based on amyloid fibrils that are tailored to promote interactions with a wide variety of cell types.


Assuntos
Amiloide/metabolismo , Células/citologia , Células/metabolismo , Nanoestruturas/química , Células 3T3 , Amiloide/química , Amiloide/ultraestrutura , Animais , Adesão Celular , Ligantes , Camundongos , Microscopia Eletrônica de Transmissão , Peptídeos/síntese química , Peptídeos/química , Peptídeos/metabolismo , Difração de Raios X
13.
Laryngoscope ; 118(3): 472-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18091331

RESUMO

BACKGROUND: Human laryngeal muscles are composed of fibers that express type I, IIA, and IIX myosin heavy chains (MyHC), but the presence and quantity of atypical myosins such as perinatal, extraocular, IIB, and alpha (cardiac) remain in question. These characteristics have been determined by biochemical or immunohistologic tissue sampling but with no complementary evidence of gene expression at the molecular level. The distribution of myosin, the main motor protein, in relation to structure-function relationships in this specialized muscle group will be important for understanding laryngeal function in both health and disease. OBJECTIVES: We determined the quantity of MyHC genes expressed in human posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscle using real-time quantitative reverse-transcriptase polymerase chain reaction in a large number of samples taken from laryngectomy subjects. The PCA muscle was divided into vertical (V) and horizontal (H) portions for analysis. RESULTS AND CONCLUSIONS: No extraocular or IIB myosin gene message is present in PCA or TA, but IIB is expressed in human extraocular muscle. Low but detectable amounts of perinatal and alpha gene message are present in both of the intrinsic laryngeal muscles. In H- and V-PCA, MyHC gene amounts were beta greater than IIA greater than IIX, but amounts of fast myosin RNA were greater in V-PCA. In TA, the order was beta greater than IIX greater than IIA. The profiles of RNA determined here indicate that, in humans, neither PCA nor TA intrinsic laryngeal muscles express unique very fast-contracting MyHCs but instead may rely on differential synthesis and use of beta, IIA, and IIX isoforms to perform their specialized contractile functions.


Assuntos
Músculos Laríngeos/metabolismo , Cadeias Pesadas de Miosina/genética , RNA/análise , RNA/biossíntese , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade
14.
Protein Sci ; 16(9): 1984-98, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17660262

RESUMO

The multifunctional protein, beta-catenin, has essential roles in cell adhesion and, through the Wnt signaling pathway, in controlling cell differentiation, development, and generation of cancer. Could distinct molecular forms of beta-catenin underlie these two functions? Our single-molecule force spectroscopy of armadillo beta-catenin, with molecular dynamics (MD) simulation, suggests a model in which the cell generates various forms of beta-catenin, in equilibrium. We find beta-catenin and the transcriptional factor Tcf4 form two complexes with different affinities. Specific cellular response is achieved by the ligand binding to a particular matching preexisting conformer. Our MD simulation indicates that complexes derive from two conformers of the core region of the protein, whose preexisting molecular forms could arise from small variations in flexible regions of the beta-catenin main binding site. This mechanism for the generation of the various forms offers a route to tailoring future therapeutic strategies.


Assuntos
Simulação por Computador , beta Catenina/metabolismo , Silicatos de Alumínio/química , Sequência de Aminoácidos , Sítios de Ligação , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Glutationa Transferase/metabolismo , Histidina/química , Peroxidase do Rábano Silvestre/imunologia , Peroxidase do Rábano Silvestre/metabolismo , Ligantes , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos , Eletricidade Estática , Propriedades de Superfície , Fatores de Transcrição TCF/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição , beta Catenina/química , beta Catenina/ultraestrutura
15.
Nanomedicine ; 2(1): 42-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17292115

RESUMO

Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade, driven by an attempt to bring radical solutions to areas of unmet medical need. What is true in the United States is also being fulfilled in Europe. This, though, is generally at a significantly lower investment level, even if for "large" capital infrastructure and interdisciplinary centers. Against this, the United Kingdom and its European partners are following the maxim "small is beautiful" and are attempting to identify and develop academic research and commercial businesses in areas that traditional nanotechnology developments involving engineering or physics find challenging. Thus in London-University College London (UCL) in a major joint project with Imperial College and linked to other UK and European centers of excellence-we are building upon our internationally competitive medical research (the two universities together form one of the largest centers of biomedical research outside the United States) to focus on and develop medical nanotechnology as a major sector of our research activity. A novel approach to commercialization has been the establishment with government and private equity funds of a "BioNanotechnology Centre" that will act as a portal for UK industry to access specialist skills to solve issues relating to developing nanotechnology-based medical applications, for example, for environmental screening, diagnostics, and therapy. This article reviews our academic and business strategy with examples from our current biomedical research portfolio.


Assuntos
Academias e Institutos/organização & administração , Pesquisa Biomédica/organização & administração , Nanomedicina/organização & administração , Pesquisa/organização & administração , Transferência de Tecnologia , Universidades/organização & administração , Reino Unido
16.
J Bone Miner Res ; 20(12): 2264-70, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16294279

RESUMO

UNLABELLED: We report on a case of osteoclast-poor osteopetrosis who received a hematopoietic stem cell graft and, despite hematological engraftment, showed little signs of response in the skeletal defect. Clinical and laboratory studies supported the concept that the bone microenvironment remained abnormal, thus reducing the clinical response to transplantation. INTRODUCTION: Osteopetrosis is a rare genetic disorder characterized by severely reduced bone resorption resulting from a defect in either osteoclast development (osteoclast-poor osteopetrosis) or activation (osteoclast-rich osteopetrosis). Patients with osteoclast-rich osteopetrosis can be rescued by allogenic hematopoietic stem cell transplantation; however, little information exists concerning the success of transplantation as a treatment for osteoclast-poor osteopetrosis. We report on a child with osteoclast-poor osteopetrosis whose diagnosis was delayed, consequently receiving a cord blood transplant from an unrelated donor at the age of 8 years. Engraftment was deemed successful by peripheral blood genotyping, although >3 years after transplantation there was little rescue of the skeletal defect and anemia, and extramedullary hematopoiesis persisted. MATERIALS AND METHODS: Peripheral blood mononuclear cells from the osteopetrosis patient, before and after transplantation, were used to generate osteoclasts in vitro in the presence of macrophage colony-stimulating factor (M-CSF) and RANKL. RESULTS: Before transplantation few, small mononuclear osteoclasts formed (F-actin ring-positive cells, co-localizing with vitronectin receptor [alphavbeta3 integrin] and TRACP) associated with occasional, small resorption lacunae. Low levels of collagen C-terminal telopeptide (CTx) fragments were released from these cultures as assessed by ELISA (CrossLaps; patient, 12.85 nM; control, 448.6 nM). In contrast, osteoclasts formed in cultures after transplantation formed to a similar degree to control cultures from healthy individuals: large numbers of osteoclasts containing numerous nuclei were present, and approximately 50% of the surface of bone slices was resorbed, associated with intermediate levels of collagen fragment release (116.48 nM). The culture data reflect the histopathology and radiological findings and also support previous studies showing that neither M-CSF nor RANKL rescues osteoclast-poor osteopetrosis. CONCLUSIONS: This is the first case reported in which a successful hematopoietic engraftment failed to correct an osteopetrotic skeletal defect, and this finding may be credited to the age at which the child was transplanted.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Osteoclastos/patologia , Osteopetrose/terapia , Fosfatase Ácida/análise , Biópsia , Antígeno CD11c/análise , Antígenos CD18/análise , Proteínas de Transporte/farmacologia , Cartilagem/patologia , Diferenciação Celular/efeitos dos fármacos , Criança , Colágeno/metabolismo , Colágeno Tipo I , Análise Mutacional de DNA , Feminino , Fêmur/patologia , Glicoproteínas/sangue , Doenças Hematológicas/etiologia , Humanos , Úmero/patologia , Integrina alfaVbeta3/análise , Isoenzimas/análise , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Glicoproteínas de Membrana/farmacologia , Osteoclastos/química , Osteoclastos/metabolismo , Osteopetrose/complicações , Osteopetrose/patologia , Osteoprotegerina , Peptídeos/metabolismo , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptores Citoplasmáticos e Nucleares/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fosfatase Ácida Resistente a Tartarato , Transplante Homólogo , Resultado do Tratamento
17.
Ultramicroscopy ; 105(1-4): 79-89, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16125320

RESUMO

Mineralised tissues such as bone consist of two material phases: collagen protein fibrils, secreted by osteoblasts, form model structures for subsequent deposition of mineral, calcium hydroxyapatite. Collagen and mineral are removed in a three-dimensional manner by osteoclasts during bone turnover in skeletal growth or repair. Bone active drugs have recently been developed for skeletal diseases, and there is revived interest in changes in the structure of mineralised tissues seen in disease and upon treatment. The resolution of atomic force microscopy and use of unmodified samples has enabled us to image bone and dentine collagen exposed by the natural process of cellular dissolution of mineralised matrix. The morphology of bone and dentine has been analysed when fully mineralised and after osteoclast-mediated bone resorption, and compared with results from other microscopy techniques. Banded type I collagen, with 66.5+/-1.4 nm axial D-periodicity and 62.2+/-7.0 nm diameter, has been identified within resorption lacunae in bone and 69.4+/-4.3 nm axial D-periodicity and 140.6+/-12.4 nm diameter in dentine substrates formed by human and rabbit osteoclasts, respectively. This observation suggests a route by which the material and morphological properties of bone collagen can be analysed in situ, compared with collagen from non-skeletal sites, and contrasted in diseases of medical importance, such as osteoporosis, where skeletal tissue is mechanically weakened.


Assuntos
Reabsorção Óssea/metabolismo , Osso e Ossos/ultraestrutura , Colágeno/ultraestrutura , Dentina/ultraestrutura , Microscopia de Força Atômica , Osteoclastos/metabolismo , Fosfatase Ácida , Animais , Imunofluorescência , Humanos , Isoenzimas , Microscopia Confocal , Microscopia Eletrônica de Varredura , Osteoclastos/ultraestrutura , Coelhos , Fosfatase Ácida Resistente a Tartarato
18.
J Periodontol ; 76(7): 1106-12, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16018753

RESUMO

BACKGROUND: Multiple idiopathic root resorption (MIRR) is a rare condition in man characterized by cervical resorption leading to significant tooth loss. A similar condition, feline osteoclastic resorptive lesions (FORL), affects up to 70% of domestic cats and thus provides a valuable model for investigating the etiopathogenesis of MIRR. The aim of the present study was to establish changes in the surface microanatomy of the tooth in late stage FORL and to identify whether its location has a surface bias. METHODS: Scanning electron microscopy (SEM) was used to analyze the surface features of enamel and cementum of feline teeth affected with advanced FORL. RESULTS: Resorption involved the coronal root at the cementoenamel junction (CEJ) in 95% of teeth and focal resorption of intact enamel was observed in 14% of teeth. In 55% of teeth, the main lesion was on the buccal surface and a distinct circumferential resorption "front" was present at the apical margin of resorption. The root surfaces of most affected teeth either lacked extrinsic fibers or cellular lacunae or featured evidence of cementum remodeling. Woven bone-like tissue was found within lesions, on resorbed dentin, or on the root surface in 27% of teeth. CONCLUSIONS: This study demonstrates that most FORL involve the CEJ, and the presence of focal lesions at this site suggests that this is where resorption is initiated. This implies that local factors in the oral microenvironment play a role in the etiopathogenesis of this condition. The study also shows that FORL are more likely to occur on buccal surfaces and are associated with changes in the microarchitecture of the root surface consistent with destruction of the normal periodontal attachment and stimulation of a reparative response. These findings may be relevant to understanding the etiopathogenesis of multiple idiopathic resorption areas in man.


Assuntos
Doenças do Gato/patologia , Reabsorção da Raiz/veterinária , Animais , Gatos , Cemento Dentário/patologia , Esmalte Dentário/patologia , Microscopia Eletrônica de Varredura , Osteoclastos , Reabsorção da Raiz/patologia , Colo do Dente
19.
Ann Otol Rhinol Laryngol ; 111(2): 120-7, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11860063

RESUMO

Myosin description in human laryngeal muscles is incomplete, but evidence suggests the presence of type I, IIA, IIX, and tonic myosin heavy chain (MHC) fibers. This study describes the unloaded shortening velocity (V0) of chemically skinned laryngeal muscle fibers measured by the slack test method in relation to MHC content. Skeletal fibers from human laryngeal and limb muscle biopsy specimens were obtained for determination of V0, and subsequently, glycerol-sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to determine the MHC isoform content. The fibers from human limb muscle had shortening speeds similar to those in previous reports on human skeletal fibers. Type I, IIA, and IIX fibers of laryngeal muscle had shortening speeds similar to those of fibers from limb muscle, but laryngeal fibers with heterogeneous MHC expression had a wide range of shortening speeds, some being nearly twice as fast as limb fibers. In addition, MHC isoform bands from human extraocular muscle comigrated with some bands from laryngeal muscle--a finding suggesting that extraocular myosin may also be expressed.


Assuntos
Músculos Laríngeos/fisiologia , Contração Muscular , Fibras Musculares Esqueléticas/fisiologia , Cadeias Pesadas de Miosina/análise , Adulto , Idoso , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Immunoblotting , Técnicas In Vitro , Músculos Laríngeos/química , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/química , Músculo Esquelético/química , Músculo Esquelético/fisiologia , Isoformas de Proteínas
20.
J Voice ; 17(1): 63-75, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12705819

RESUMO

The human posterior cricoarytenoid (PCA) muscle is divided into two compartments, the vertical and horizontal bellies, which contain differences in their myosin heavy chain (MyHC) composition. Using immunohistochemical techniques on whole PCA samples, this study provides a more thorough description of the fiber type composition of entire bellies of the PCA. Four patients provided complete PCA samples containing both compartments of their right and left sides; two with unilaterally immobilized vocal folds. The horizontal belly had 80% slow (type I) fibers and 20% fast (type II) fibers. The vertical belly contained equal amounts of slow and fast fibers (approximately 55%:45%); clearly distinguishing between two compartments. Atrophy of muscle fibers and fiber type grouping were also present in both normal and affected subjects; providing no clear confirmation of the clinical findings of vocal fold immobilization. Further study of the PCA muscle from patients with unilaterally immobilized vocal folds is needed.


Assuntos
Cartilagem Aritenoide , Cartilagem Cricoide , Músculos Laríngeos/patologia , Fibras Musculares Esqueléticas/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Paralisia das Pregas Vocais/patologia , Idoso , Atrofia/patologia , Técnicas de Cultura , Feminino , Humanos , Imuno-Histoquímica , Músculos Laríngeos/fisiopatologia , Laringectomia , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Paralisia das Pregas Vocais/fisiopatologia , Paralisia das Pregas Vocais/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA