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1.
J Intern Med ; 287(6): 592-608, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32463135

RESUMO

Mitochondrial medicine is a field that expanded exponentially in the last 30 years. Individually rare, mitochondrial diseases as a whole are probably the most frequent genetic disorder in adults. The complexity of their genotype-phenotype correlation, in terms of penetrance and clinical expressivity, natural history and diagnostic algorithm derives from the dual genetic determination. In fact, in addition to the about 1.500 genes encoding mitochondrial proteins that reside in the nuclear genome (nDNA), we have the 13 proteins encoded by the mitochondrial genome (mtDNA), for which 22 specific tRNAs and 2 rRNAs are also needed. Thus, besides Mendelian genetics, we need to consider all peculiarities of how mtDNA is inherited, maintained and expressed to fully understand the pathogenic mechanisms of these disorders. Yet, from the initial restriction to the narrow field of oxidative phosphorylation dysfunction, the landscape of mitochondrial functions impinging on cellular homeostasis, driving life and death, is impressively enlarged. Finally, from the clinical standpoint, starting from the neuromuscular field, where brain and skeletal muscle were the primary targets of mitochondrial dysfunction as energy-dependent tissues, after three decades virtually any subspecialty of medicine is now involved. We will summarize the key clinical pictures and pathogenic mechanisms of mitochondrial diseases in adults.


Assuntos
Doenças Mitocondriais/genética , Adulto , Reparo do DNA/genética , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Humanos , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/diagnóstico , Mutação/genética
2.
J Orthop Traumatol ; 15(3): 181-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24671489

RESUMO

BACKGROUND: Posterior wall fracture is the most common acetabular fracture. Comminuted fractures with an impacted segment represent a subtype of this injury. The subchondral bone of the articular zone is compressed and causes a bone defect. The impacted fragment should be isolated, mobilized, and then reduced. A bone graft should be used to fill the gap. The other fragments are fixed following the reduction of the impacted segment. MATERIALS AND METHODS: Ten patients with comminuted fractures and impacted segments with bone defects were enrolled in our study, from January 2010 to July 2012. Autogenous bone grafts from the greater trochanter were used to fill the gap in all patients. The reduction was achieved through the insertion of the graft above the impacted fracture, and plate fixation was performed subsequently. Merle d'Aubigne and Postel scoring, modified by Matta, was applied to evaluate the patients during follow-up. The mean follow-up was 12 months. RESULTS: The clinical results included one "excellent", four "very good", four "good" and one "poor". Pain in the zone of graft harvesting was not detected in any patient. Femoral head necrosis was observed in one case. No other severe complications were detected. CONCLUSIONS: Using an autogenous bone graft to fill the bone defect supplies excellent mechanical stability without any severe complications at the donor site. This surgical technique seems to be effective and safe in treating a comminuted fracture of the posterior wall in association with an impacted segment. LEVEL OF EVIDENCE: Level IV.


Assuntos
Acetábulo/lesões , Transplante Ósseo , Fêmur/transplante , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Cominutivas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Feminino , Fraturas Cominutivas/complicações , Luxação do Quadril/complicações , Luxação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Nutr Metab Cardiovasc Dis ; 23(8): 771-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22770750

RESUMO

AIM: The study was aimed to evaluate the influence of gender on left ventricular (LV) remodeling in metabolic syndrome (MetS). METHODS AND RESULTS: We enrolled 200 subjects without diabetes or overt cardiovascular diseases, never treated with anti-hypertensive drugs or statins: 60 men and 40 women with MetS matched by age, gender and 24 h systolic and diastolic blood pressure (BP) with 60 men and 40 women without MetS. The patients underwent blood tests, 24 h our BP monitoring, LV echocardiographic examination. LV mass indexed by eight(2.7) was significantly greater in men and women with MetS than without MetS. Compared with women without MetS, women with MetS had significantly higher posterior wall thickness and relative wall thickness, greater prevalence of LV concentric remodeling/hypertrophy and lower indices of LV diastolic function, whereas all these parameters were not significantly different between men with and without MetS. MetS was an independent predictor of relative wall thickness and LV mass index in women, but not in men. CONCLUSION: The impact of MetS on LV remodeling is significantly influenced by gender: the effects of MetS are more pronounced in women, with development of LV concentric hypertrophy/remodeling and preclinical diastolic dysfunction.


Assuntos
Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Síndrome Metabólica/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Antropometria , Pressão Sanguínea , Estudos de Casos e Controles , Diabetes Mellitus , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Função Ventricular Esquerda/fisiologia
4.
J Enzyme Inhib Med Chem ; 28(2): 289-93, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22299577

RESUMO

4-Sulfamoyl-N-(3-morpholinopropyl)benzamide (I-1), N-(3-morpholinopropyl)benzene-1,4-disulfonamide (I-2) and N-(4-diethylaminoethoxybenzyl)benzene-1,4-bis(sulfonamide (I-3), were prepared and assayed as inhibitors of four carbonic anhydrase (CA) isoenzymes hCA I, hCA II, hCA IV and hCA XII. These compounds exhibited nanomolar half maximal inhibitory concentration (IC(50)) ranging from 58 to 740 nmol/L. All three aromatic sulfonamides show different activities for the isoenzymes studied with lowest affinity against isoenzyme hCA XII.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Sulfonamidas/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/isolamento & purificação , Isoformas de Proteínas/metabolismo , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
5.
Acta Radiol ; 54(7): 749-56, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23550187

RESUMO

BACKGROUND: The main causes of renal artery stenosis (RAS) are atherosclerosis and fibromuscular dysplasia. Despite contrast-enhanced magnetic resonance angiography (CE-MRA) being a safe and reliable method for diagnosis of RAS especially in young individuals, recently it has been possible to adopt innovative technologies that do not require paramagnetic contrast agents. PURPOSE: To assess the accuracy of steady-state free-precession (SSFP) non-contrast-enhanced magnetic resonance angiography (NC-MRA) by using a 1.5 T MR scanner for the detection of renal artery stenosis, in comparison with breath-hold CE-MRA as the reference standard. MATERIAL AND METHODS: Sixty-three patients (33 men, 30 women) with suspected renovascular hypertension (RVHT) were examined by a 1.5T MR scanner; NC-MRA with an electrocardiography (ECG)-gated SSFP sequence was performed in 58.7% (37/63) of patients; in 41.3% (26/63) of patients a respiratory trigger was used in addition to cardiac gating. CE-MRA, with a three-dimensional gradient echo (3D-GRE) T1-weighted sequence, was performed in all patients within the same session. Maximum intensity projection (MIP) image quality, number of renal arteries, and the presence of stenosis were assessed by two observers (independently for NC-MRA and together for CE-MRA). The agreement between NC-MRA and CE-MRA as well as the inter-observer reproducibility were calculated with Bland-Altman plots. RESULTS: MIP image quality was considered better for NC-MRA. NC-MRA identified 143 of 144 (99.3%) arteries detected by CE-MRA (an accessory artery was not identified). Fourteen stenoses were detected by CE-MRA (11 atherosclerotic, 3 dysplastic) with four of 14 (28.5%) significant stenosis. Bland-Altman plot demonstrated an excellent concordance between NC-MRA and CE-MRA; particularly, the reader A evaluated correctly all investigated arteries, while over-estimation of two stenoses occurred for reader B. Regarding NC-MRA, inter-observer agreement was excellent. CONCLUSION: NC-MRA is a valid alternative to CE-MRA for the assessment of renal arteries.


Assuntos
Angiografia por Ressonância Magnética/métodos , Obstrução da Artéria Renal/diagnóstico , Artéria Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Imagem de Sincronização Cardíaca , Meios de Contraste , Feminino , Humanos , Hipertensão Renovascular/complicações , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Obstrução da Artéria Renal/etiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Waste Manag ; 144: 336-348, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429871

RESUMO

Air pollution control residues (APCr) are hazardous materials generated from municipal solid waste incineration and require appropriate management. This life cycle assessment (LCA) study investigates the environmental impacts of current and alternative management options, considering the possibility of a cascading management of APCr, where one treatment technology is followed by another. In total, 14 base case scenarios and 30 sensitivity scenarios were evaluated. The effects of APCr composition, leaching, time horizon, and uncertainties were investigated. The APCr management options with the lowest environmental impacts and the smallest uncertainties were i) backfilling of underground salt mines and ii) neutralization treatment followed by backfilling (Langøya, Norway). These options were followed by iii) scenarios that included Zn extraction, iv) cement stabilization of fresh APCr followed by landfilling and v) production of cement aggregates made from carbonated APCr followed by their utilization in construction works. Recovery of salts from APCr required further performance optimizations before being environmentally competitive with other options. Long-term leaching emissions of Zn, Cr and As were among the largest contributors to toxicity-related impacts, emphasizing the need for management strategies that minimize their leaching. The investigated scenarios demonstrate that increased "processing" and cascading utilization of the residues, contribute with increased uncertainty of the results compared to landfilling and may not necessarily lead to decreased environmental impacts. LCA studies of APCr management should address the full management chain, rather than just the first treatment. Overall, the results of this study were found robust, also considering potential changes in the surrounding energy system.


Assuntos
Incineração , Eliminação de Resíduos , Animais , Conservação dos Recursos Naturais , Estágios do Ciclo de Vida , Resíduos Sólidos/análise , Tecnologia
7.
Waste Manag ; 83: 113-122, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30514457

RESUMO

In Denmark, increasing amounts of woody biomass are being used for the production of renewable energy, resulting in more wood ashes being generated. While these materials have been mainly landfilled, wood ashes may also be utilised for fertilizing and liming purposes on top of soils. Pre-treatments involving hardening or granulation may be carried out prior to soil application. In this study, two Danish wood ash samples were hardened and/or granulated. Lab-hardening induced rapid changes in the shape of the acid neutralisation capacity curve of the ashes. Up-flow column tests, assuming local equilibrium conditions, were employed to investigate the leaching from pre-treated ashes. Granules and loose ashes demonstrated similar leaching behaviours, indicating that similar geochemical processes were governing their leaching. In comparison with untreated fresh ashes, the hardened ashes demonstrated reduced leaching of Ca, Ba, Pb and Zn with concentration levels generally below or close to the analytical limits of quantification; to the contrary, the leaching of As, P, Sb, Si, V and Mg was enhanced in the hardened ashes. The release of alkalinity was reduced by hardening. In general, all granules were barely breakable by finger-pinching and they could withstand one month of continuous leaching, preserving their overall shape. The solubility of phosphorous in neutral ammonium citrate indicated that about 30-51% of the total P content in the ash samples was released, suggesting that the ashes could be potentially valuable as P-fertiliser if applied onto soil.


Assuntos
Cinza de Carvão , Incineração , Biomassa , Dinamarca , Solo
8.
Waste Manag ; 74: 373-383, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29246665

RESUMO

With increasing amounts of woody biomass being combusted for energy purposes worldwide, more wood ash is being generated and needs management. As an alternative to landfilling, residues may be utilised for liming and fertilising purposes on forest soils. Comprehensive evaluations of long-term leaching from these residues are needed in order to assess potential environmental impacts associated with their utilisation. Two Danish wood ash samples, one fly ash and one mixed ash (a combination of fly ash and bottom ash), were evaluated in long-term percolation column tests (up to L/S ∼2000 L/kg), in order to quantify the release of major, minor and trace metal(loid)s. While columns of three different lengths were used, the leaching of individual elements could be described as a function of the L/S ratio - irrespective of the column length. At L/S 1000 L/kg, the cumulative releases of K, S, Na, Ca and Rb were at 40-100% of their respective solid contents, followed by Ba, Cr, Sb, Sr and V at 15-40% and Al, Mg, Zn, Cd, Co, Fe, Pb, Tl, Mn and P at < 5%. Speciation calculations indicated that (i) the observed concentrations of Ca, Mg, Al, Ba, Si and sulphate from both ash types could be described through the dissolution/precipitation of a limited set of minerals and that (ii) leaching of silicates should be included in long-term assessment of alkalinity release from wood ashes. Non-equilibrium conditions were indicated by flow interruptions. However, the presence of non-equilibrium did not have significant effect on the calculated cumulative releases at high L/S ratios. Based on the assessment of cumulative releases at L/S 10 L/kg and L/S 1000 L/kg it is concluded that low L/S-based data may not provide sufficient background for prediction of long-term release from wood ash, in particular for Ba, Cr, Sb and V, and less critically also for As, Cd, Cu, Mo and Ni.


Assuntos
Cinza de Carvão , Oligoelementos/química , Biomassa , Incineração , Solo
9.
Injury ; 49 Suppl 4: S2-S8, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30526947

RESUMO

This case report describes the management and therapeutic solution for the treatment of subtrochanteric non-union in a patient with hip arthrodesis. Two techniques can be used in the treatment of these non-unions: a closed intramedullary nailing or an open technique with plate, preferably carried out together with cortical bone graft. The surgical technique varies depending on the fixation method used for the initial treatment of the fracture and on the characteristics of the non-union. We report an unusual case of a patient who started her long clinical history more than 40 years ago with a septic arthritis of the hip healed in arthrodesis. 35 years later, after having undergone various surgeries, she fractured the proximal femur, which had to be operated seven times before reaching healing. Satisfactory outcomes were finally obtained. Arthrodesis proved to be the main cause of failed healing and of the recurrent non-union.


Assuntos
Artrodese/efeitos adversos , Transplante Ósseo/métodos , Fraturas do Fêmur/cirurgia , Consolidação da Fratura/fisiologia , Fraturas não Consolidadas/cirurgia , Fraturas do Quadril/cirurgia , Reoperação/estatística & dados numéricos , Pinos Ortopédicos , Placas Ósseas , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Fixação Intramedular de Fraturas , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/patologia , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/patologia , Humanos , Pessoa de Meia-Idade , Reoperação/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Waste Manag ; 70: 127-138, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28947146

RESUMO

In Denmark, increasing amounts of wood ashes are generated from biomass combustion for energy production. The utilisation of ashes on top of forest soil for liming purposes has been proposed asan alternative to landfilling. Danish wood ash samples were collected and characterised with respect to chemical composition, mineralogy and leaching properties (batch leaching at L/S 2 and 10L/kg, and pH-dependent leaching at 10L/kg). Large variations in the ash liming properties were observed (ANC7.5: 1.8-6.4meqH+/g), indicating that similar soil application dosages may result in different liming effects. High contents of Ca, Si, P, K and Mg were observed in all samples, while the highest contents of S and N were found in fly ashes and mixed ashes (combination of fly and bottom ashes). Similarly, the highest contents of some trace metals, e.g. Cd, Mo and Se, were observed for fly ash. Releases of major, minor and trace elements were affected significantly by pH: high releases of PO43-, Mg, Zn, Cu and Cd were found for acidic conditions relevant to forest soils, while the highest releases of Mo and Cr were observed in alkaline conditions. Mineral phases were selected based on XRD analyses and the existing literature, and they were applied as inputs for the geochemical modelling of pH-dependent leaching. Mineral dissolution was found adequate for a wide range of major elements and nutrients, while the description of trace elements could be done only for parts of the pH-range. Content and leaching of PAHs were observed below detection limits. The source-term release of Ca, K, Mg, Mn, and P in acidic conditions relevant to forest soils was higher than ten years of atmospheric deposition, in contrast to the relatively low release of Al, Fe and Na. The potential release of Cd was found to be the most critical element compared with soil quality criteria, whereas the maximum theoretical loads of Ba, Cd, Cr, Sr, Mo, Ni, Pb, Sb, Se, Sn and V were relatively low.


Assuntos
Incineração/métodos , Resíduos/análise , Biomassa , Dinamarca , Florestas , Concentração de Íons de Hidrogênio , Metais/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo/química , Poluentes do Solo/análise , Oligoelementos/análise
11.
Musculoskelet Surg ; 101(Suppl 2): 105-112, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29052035

RESUMO

AIM: The aim of this study was to evaluate nonunion causes of surgically treated humeral shaft fractures in two different trauma centers. METHODS: A total of 327 cases of humeral shaft fractures were treated in 11 years in two trauma centers. We retrospectively reviewed in detail some factors in order to understand the reasons for nonunion: (1) fracture type, according to the AO classification, (2) grade of open fracture, according to Gustilo-Anderson, (3) timing, (4) reduction and (5) fixation. RESULTS: We observed 19 nonunions, 10 women and 9 men, with an average age of 57 years. Fractures were 1 A1 case, 2 A2 cases, 4 B2 cases, 6 B3 cases, 2 C1 cases, 1 C2 case and 3 C3 cases. Three cases had a simple fracture with two fragments; all the other were comminuted. Fifteen cases were closed, four open. The major criticalities observed were fracture comminution, exposure, unstable fixation and bone resorption. All 19 patients with nonunion underwent surgical fixation with compression plate and frozen cortical bone graft. A 4.5 LCP plate was used in 17 cases. The remaining 2 cases had an anatomical site-specific proximal humeral 3.5-mm LCP plate (Synthes, Paoli, PA, USA). In 17 patients, the nonunion healed: 15 cases treated with a 4.5 straight plate, and 2 cases with an anatomical site-specific proximal humeral 3.5 mm LCP plate, at a mean of 5 months. In 2 cases, consolidation was not reached. CONCLUSIONS: We believe that humeral diaphyseal fractures should be treated surgically to avoid many complications. Our retrospective analysis indicates that factors that lead to a fixation failure are fracture comminution, open fracture, unstable fixation. The 19 nonunions treated with compression plating and frozen bone graft demonstrated consolidation in almost 90% of the cases.


Assuntos
Consolidação da Fratura , Fraturas Cominutivas/cirurgia , Fraturas não Consolidadas/etiologia , Fraturas do Úmero/cirurgia , Centros de Traumatologia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Reabsorção Óssea , Transplante Ósseo , Feminino , Fixação de Fratura/métodos , Fraturas Fechadas/cirurgia , Fraturas Expostas/cirurgia , Fraturas não Consolidadas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
12.
Musculoskelet Surg ; 100(Suppl 1): 97-104, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27521146

RESUMO

PURPOSE: Distal-third diaphyseal fractures of the humerus are often hard to treat due to location and pattern of the fractures, radial nerve injury, and quality of bone and age of patients. The aim of this retrospective study is to propose the best approach and the best surgical technique according to the pattern of extra-articular fracture of the distal humerus. METHODS: We have treated 37 fractures of the distal humerus between January 2010 and July 2015 classified according to the AO classification. There were 2 open fractures. We treated all fractures with open reduction and internal fixation with plates and screws. In 20 cases, we performed a posterior midline triceps-splitting approach, with patients in prone decubitus position; in 2 cases, the triceps-splitting approach with the patients in supine decubitus position; in 3 cases, the olecranon osteotomy approach in prone decubitus position; and in 12 cases, the lateral approach in supine decubitus position. RESULTS: Thirty cases had a medium follow-up of 6 months. We observe 2 post-operative radial nerve palsies healed in 5 months and 2 cases of non-union. The average time to union of remaining cases was 16 weeks (range 12-24). Elbow motility was complete in 25 cases, in 4 cases there was an extension loss of 5°, and in one case there was an extension loss of 10°. CONCLUSIONS: The use of plates allows an anatomical fracture reduction, a better control of alignment of humerus and, with a rigid fixation, an early elbow mobilization. The best approach and the best surgical technique depend on the pattern of the fracture of distal humerus.


Assuntos
Placas Ósseas , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas do Úmero/cirurgia , Nervo Radial/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Musculoskelet Surg ; 100(1): 1-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26667625

RESUMO

PURPOSE: The incidence of trochanteric fractures has increased significantly during the last few decades, especially in elderly patients with osteoporosis. The dynamic/sliding hip screw and the cephalomedullary nail are the most commonly used fixation methods to treat trochanteric fractures. The improvements in the Gamma Nail System (GNS) associated with a correct surgical technique reduced the postoperative orthopedic complications. The purpose of this study was to compare the results of the different Gamma Nails. METHODS: The present study is a retrospective analysis of 2144 patients treated with GNS between January 1997 and December 2011 for trochanteric fractures, classified according to AO classification method. The patients were divided into three groups according to the nailing system: 525 were treated with Standard Gamma Nail (SGN), 422 with Trochanteric Gamma Nail (TGN) and 1197 with Gamma3 Nail. RESULTS: The overall incidence of intra-operative complications was 1.21 %; the incidence of intra-operative complications for each group was 1.71 % for SGN group, 0.47 % for TGN group and 1.25 % for Gamma3 Nail group. The overall incidence of postoperative complications was 5.48 %, and the incidence for each group was 10.73 % for SGN group, 9.92 % for TGN group and 2.92 % for Gamma3 Nail group. CONCLUSION: The GNS is a safe device with a low rate of intra-operative complications. The evolution of this nail system reduces postoperative complications, thus improving the results at follow-up and confirming that the Gamma3 Nail is a safe and predictable device to fix trochanteric fracture.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Parafusos Ósseos , Humanos , Estudos Retrospectivos
14.
Biochim Biophys Acta ; 429(2): 538-45, 1976 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-4135

RESUMO

Four major forms of alpha-fucosidase (EC 3.2.1.51) activity were separated by isoelectrofocusing from sera of normal control individuals. All forms shifted towards less acidic pI values after neuraminidase treatment. In two patients affected with fucosidosis, only a single major acidic peak was observed and this was affected to a lesser degree by neuraminidase treatment. The kinetics of heat inactivation of the residual activity found in these two patients showed two decay rates while the controls showed only one rate. These data are considered in relation to the hypothesis of the existence of interconvertible thermolabile and thermostable forms of the enzyme which has been discussed in the preceeding paper. The residual alpha-fucosidase found in patients could be structurally altered so that its ability to form the thermostable higher molecular weight aggregates is impaired.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/enzimologia , Dissacaridases/deficiência , Fucose/metabolismo , Isoenzimas/deficiência , alfa-L-Fucosidase/deficiência , Adolescente , Criança , Feminino , Fibroblastos/enzimologia , Humanos , Concentração de Íons de Hidrogênio , Focalização Isoelétrica , Isoenzimas/isolamento & purificação , Isoenzimas/metabolismo , Cinética , Masculino , Neuraminidase , Temperatura , alfa-L-Fucosidase/isolamento & purificação , alfa-L-Fucosidase/metabolismo
15.
J Mol Biol ; 164(4): 493-511, 1983 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-6302277

RESUMO

Three different cloned segments of African green monkey DNA that contain alpha-satellite sequences linked to a previously undescribed, distinct monkey satellite (called deca-satellite) are described here. The cloned segments were derived from a monkey DNA library in lambda Charon 4A that was constructed to select for junctions between alpha-satellite and other DNA sequences. The structure of the deca-satellite and of a junction between deca-satellite and alpha-satellite were studied by subcloning appropriate fragments of the original cloned segments and by sequence analysis. Deca-satellite has a ten base-pair repeat unit; the consensus sequence of the repeat units is 5' A-A-A-C-C-G-G-N-T-C. Sequences homologous to the deca-satellite are in the middle repeated class of genomic DNA. Analysis of the organization of deca-satellite sequences by digestion of total DNA with various restriction endonucleases and hybridization with a cloned deca-satellite probe revealed extensive polymorphism in the genomes of different individual monkeys but not among the tissues of one organism. These observations indicate that the arrangement of deca-satellite sequences is continually changing. An unusual alpha-satellite repeat unit occurs at a junction between the alpha-satellite and deca-satellite. It resembles the major baboon alpha-satellite more closely than it does monkey alpha-satellite and thereby provides evidence in favor of the "library" hypothesis for satellite evolution.


Assuntos
DNA Satélite , Genes , Animais , Sequência de Bases , Chlorocebus aethiops , Enzimas de Restrição do DNA , DNA Recombinante , Desoxirribonucleotídeos/análise , Eletroforese em Gel de Ágar , Polimorfismo Genético
16.
J Mol Biol ; 179(4): 629-49, 1984 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-6094831

RESUMO

Previously we reported the existence of a highly polymorphic satellite, deca-satellite, in the African green monkey genome; deca-satellite probe anneals to complex sets of repeated restriction endonuclease fragments that differ from individual to individual in the monkey population. Here we present experiments aimed at clarifying the structure and organization of deca-satellite sequences and investigating the mechanisms that generate the polymorphisms. Deca-satellite represents less than 1% of the monkey genome but the percentage varies from one monkey to another. The core sequence 5'-C-C-G-G within the ten base-pair deca-satellite repeat unit is well conserved and the central 5'-C-G is sometimes but not always methylated. Restriction endonuclease analysis with BamHI and EcoRI defines separate satellite domains that have evolved in an independent manner. In situ hybridization shows deca-satellite to be located at the centromeric regions of some but not all monkey chromosomes. This location is independently confirmed by a high frequency, in monkey libraries, of segments containing junctions between deca-satellite and alpha-satellite, the main monkey centromeric satellite. The total number of metaphase chromosomes that show centromeric grains after in situ hybridization with a deca-satellite probe varies from one monkey to another. Moreover, in situ hybridization to endoreduplicated diplochromosomes showed that deca-satellite is occasionally distributed asymmetrically on one or the other of the two pairs of sister chromatids in one diplochromosome. This indicates that major reorganization of the satellite can occur frequently in somatic cells. We discuss several possible mechanisms by which deca-satellite sequences could be either amplified or deleted during a single replicative cycle. Also, on the basis of the marked fluidity of deca-satellite abundance and organization and other well-known attributes of centromeric satellites, we suggest that the existence and maintenance of centromeric satellite rests on the role of the tandem repeats themselves and not on any particular nucleotide sequence, repeat length or organization.


Assuntos
Centrômero/análise , Cromossomos/análise , DNA Satélite , Polimorfismo Genético , Animais , Chlorocebus aethiops , Replicação do DNA , Enzimas de Restrição do DNA , DNA Satélite/genética , Eletroforese em Gel de Ágar , Metáfase , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico
17.
Chir Main ; 24(3-4): 193-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16121629

RESUMO

We report a case of leiomyoma of the finger in the right hand of a 12-year-old boy: a rare site for localization and unusual for age. This is a benign tumor originating from non-striated muscle that is very uncommon in the hand. The uterus is considered the most common location for leiomyoma and when it occurs in the extremities, it is more common in the leg, ankle and foot. It usually occurs in the third and fourth decades of life and it is rarely diagnosed before surgery as the diagnosis can only be confirmed histologically.


Assuntos
Leiomioma/diagnóstico , Neoplasias Musculares/diagnóstico , Criança , Dedos/cirurgia , Humanos , Leiomioma/cirurgia , Masculino , Neoplasias Musculares/cirurgia
18.
Cell Death Dis ; 6: e2021, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26673666

RESUMO

Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke.


Assuntos
DNA Mitocondrial/genética , Atrofia Óptica Hereditária de Leber/etiologia , Espécies Reativas de Oxigênio/metabolismo , Fumar/efeitos adversos , Fumar/genética , DNA Mitocondrial/metabolismo , Feminino , Humanos , Masculino , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/metabolismo , Atrofia Óptica Hereditária de Leber/patologia , Fosforilação Oxidativa , Fumar/metabolismo , Fumar/patologia
19.
Gene ; 50(1-3): 299-311, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3034734

RESUMO

To investigate the role of satellite DNA in eukaryotic genomes, we isolated from an African green monkey (Cercopithecus aethiops) genomic library cloned segments containing the previously described deca-satellite linked to low-copy-number genomic sequences. Three such clones were obtained. The low-copy-number sequences in the three clones do not cross-hybridize suggesting that they derive from different genomic loci. The structure of one of the clones, lambda MkA, is described in detail. Subcloned segments containing the low-copy-number sequences from lambda MkA anneal to monkey, human and mouse genomic DNA. The subcloned probes were used to select clones containing homologous sequences from a second, independent monkey library as well as from human and mouse genomic libraries. Several of the newly isolated monkey clones hybridized to probes containing the species-specific deca- and alpha-satellites, confirming the genomic association of the low-copy-number sequence in lambda MkA with satellite DNA. Moreover, several of the human and mouse clones hybridized to species-specific human and mouse satellite DNAs, respectively. These experiments indicate that the low-copy-number sequence in lambda MkA and its association with satellite DNA is conserved in primates and rodents.


Assuntos
DNA Satélite , Animais , Chlorocebus aethiops , Mapeamento Cromossômico , Clonagem Molecular , Enzimas de Restrição do DNA , Ligação Genética , Humanos , Camundongos , Homologia de Sequência do Ácido Nucleico
20.
Arch Pediatr Adolesc Med ; 154(11): 1085-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11074847

RESUMO

OBJECTIVE: To compare the completion rate of hepatitis B vaccination among adolescents who receive primary care at 2 comprehensive high school-based health centers (SBHCs) and a hospital-based adolescent health center (AHC) to assess predictors for successful immunization. METHODS: A retrospective chart review of patients seen for comprehensive history and physical examinations from September 1997 to March 1998 at 2 SBHCs and an AHC was conducted to determine the immunization status for hepatitis B. One SBHC (SBHC-A) had previously implemented an outreach strategy consisting of advertising through the school's loudspeaker, whereas the other SBHC (SBHC-B) and the AHC did not. Completion rates were assessed among all students requesting comprehensive history and physical examinations. A subset analysis among those without prior immunizations was performed. RESULTS: Of 510 records reviewed, 406 had documented data for hepatitis B immunization status, and 191 (37 for SBHC-A, 59 for SBHC-B, 95 for AHC) did not have any prior hepatitis immunizations. The completion rate of hepatitis B vaccination was significantly higher at SBHC-A (76%) compared with the other 2 sites (29% for SBHC-B and 24% for AHC) (P<.001). CONCLUSION: Patients with access to SBHC services that strongly emphasize outreach were more likely to complete the hepatitis B vaccination series.


Assuntos
Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Programas de Imunização/estatística & dados numéricos , Adolescente , Feminino , Promoção da Saúde , Humanos , Esquemas de Imunização , Masculino , Estudos Retrospectivos , Vacinação/estatística & dados numéricos
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