RESUMO
BACKGROUND: Cadmium-zinc-telluride (CZT) SPECT/CT cameras with large field of view offer a higher sensitivity than conventional Anger cameras. This prospective study aimed to determine the equivalence between a conventional protocol and a reduced acquisition time protocol for 201-Thallium myocardial perfusion imaging (MPI) using a whole-body CZT SPECT camera. METHODS AND RESULTS: Stress MPI was obtained for 103 consecutive patients on a DISCOVERY-CZT camera. Images were anonymized and post-processed to simulate a 25% (D75 dataset) and 50% (D50 dataset) decrease in total recorded counts. Concerning the number of segments displaying a tracer uptake < 70% of maximum intensity per patient, equivalence was demonstrated for both count-reduced datasets with a good inter-observer agreement (between 0.90 and 0.88). When comparing the full-vs-D75 datasets and full-vs-D50 datasets, mean difference was 0.06 segment (CI95: [- 0.15;0.27], P < 0.001) and 0.518 segment (CI95: [0.28;0.76], P < 0.001) respectively. Inter-observer agreement was also moderate to good concerning the number of pathological segments (between 0.6 and 0.7) and excellent for functional parameters. CONCLUSION: Whole-body CZT SPECT/CT cameras allow to reduce 201-Thallium MPI injected activity or acquisition time by 50% with an equivalence in the number of segments displaying a tracer uptake < 70% of maximum intensity and with a good inter-observer agreement.
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Imagem de Perfusão do Miocárdio , Cádmio , Humanos , Imagem de Perfusão do Miocárdio/métodos , Estudos Prospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Telúrio , Tálio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , ZincoRESUMO
INTRODUCTION: Moyamoya angiopathy (MMA) is a progressive steno-occlusive disease of the distal internal carotid arteries mainly described in Asia. It induces the development of collateral vascular networks to reduce chronic cerebral hypoperfusion. Symptoms depend on the patient's age in Asia: children are at greater risk of transient or constituted ischemic events, whereas adults are more exposed to hemorrhagic stroke. Data from the literature seem to show that the pattern of MMA in western countries differs from that in Asia. MATERIAL AND METHODS: A retrospective study of patients with MMA was conducted in Bourgogne-Franche-Comté (mid-eastern France). Clinical data (symptoms, risk factors, age at diagnosis, number and timing of recurrences, type of treatment) as well as radiological data (angiographic findings, Suzuki's grade) were analyzed. RESULTS: Seventeen adult patients (9 men, 53%) were followed at the university hospitals of Besançon and Dijon from 2009 to 2016. Fourteen patients (83%) had bilateral disease. The mean age at diagnosis was 49 years (±16), 83% of the patients were Caucasian and 17% originated from Maghreb. Only 17% of the hemispheres had a hemorrhagic form. Ischemic form was more frequent before diagnosis with transient ischemic attack (24% of patients) and stroke (83% of patients). With medical treatment, 9 patients suffered from stroke recurrence (53% of patients) with an average delay of 22.7±34 months. Three patients (18%) had combined surgical management by encephelo-synangiosis and superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis, without symptom recurrence after treatment with an average follow up of 14 months. CONCLUSION: MMA remains a rare cerebrovascular disease in Europe and requires multidisciplinary care. Epidemiological analysis showed differences with the Asian population, especially the predominance of ischemic forms in adults.
Assuntos
Doença de Moyamoya/epidemiologia , Doença de Moyamoya/terapia , Adolescente , Adulto , África do Norte/epidemiologia , Idade de Início , Idoso , Criança , Feminino , França/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/diagnóstico , Procedimentos Neurocirúrgicos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: Controlling prekallikrein activation by C1 inhibitor (C1Inh) represents the most essential mechanism for angioedema patient protection. C1Inh function in the plasma is usually measured based on the residual activity of the C1s protease not involved in the pathological process. We have hereby proposed an alternative enzymatic measurement of C1Inh function based on contact-phase activation and correlation with angioedema diagnostic requirements. METHODS: The contact phase was reconstituted using the purified components, with C1Inh standard or plasma sample. The kinetics of the amidase activity were monitored using Pro-Phe-Arg-pNA, independently of alpha2-macroglobulin. We prevented any interference from a possible high plasma kininogenase activity by preincubating the samples with protease inhibitor. Receiver operating characteristics (ROC) were used to calculate the assay's diagnostic performance. RESULTS: The calibration curve was built using C1Inh standard (threshold limit 0.10 × 10(-3) U, i.e., 0.2 pmol), and C1Inh function was quantified in the sample, with a reference interval established based on healthy individuals (n = 281; men: 0.61-1.10 U/ml, median: 0.85 U/ml; women: 0.42-1.08 U/ml, median: 0.74 U/ml). The median values of female donors were lower than those of the others due to estrogen, yet C1Inh function remained within the reference interval. The ROC curve calculation provided the following optimum diagnostic cutoff values: women 0.36 U/ml (area under curve [AUC]: 0.99; sensitivity: 93.48%; specificity: 99.37%); and men 0.61 U/ml (AUC: 1; sensitivity: 100.0%; specificity: 100.0%). CONCLUSION: The performance outcome provided features suitable for angioedema diagnostic or follow-up. Established by means of the kinin formation process, this assay should be preferred over the method based on a C1s protease target.
Assuntos
Proteínas Inativadoras do Complemento 1/metabolismo , Peptídeo Hidrolases/metabolismo , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/imunologia , Angioedemas Hereditários/metabolismo , Bioensaio/métodos , Bioensaio/normas , Estrogênios/metabolismo , Fator XIIa/metabolismo , Feminino , Humanos , Cininogênios/metabolismo , Masculino , Pré-Calicreína/metabolismo , Ligação Proteica , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , alfa-Macroglobulinas/metabolismoRESUMO
Kinin-mediated angioedema results from accumulation of kinins, vasoactive and vasopermeant peptides, on the vascular endothelium. The disease is characterized by sudden episodes of swelling in the subcutaneous and submucosal tissues; the edema may occur spontaneously or it may be precipitated by triggering factors such as physical or emotional stress, or certain medicines. The characterization of kinin formation and catabolism systems helps improve knowledge of the aetiopathogenic mechanisms involved and provides the basis for classification of kinin-mediated angioedema conditions; thus, we may distinguish between angioedema with C1 inhibitor deficiency, whether inherited or acquired, and angioedema with normal C1 inhibitor activity, associated with increased kinin-forming activity or deficiency in kinin catabolism enzymes. In support of the clinical diagnosis, the physician may request laboratory investigation for a functional and molecular definition of the disease. Laboratory diagnosis is based on the characterization of: (1) kinin production control by C1 inhibitor investigation (function, antigen levels and circulating species); (2) kinin production (kininogenase activity, kininogen cleavage species); and (3) kinin catabolism enzymes (aminopeptidase P, carboxypeptidase N, angiotensin-I converting enzyme and dipeptidyl peptidase IV). An abnormal biological phenotype is supported by examination of susceptibility genes (SERPING1, F12 and XPNPEP2) and mutation segregation in the families.
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Angioedema/sangue , Angioedema/diagnóstico , Cininas/sangue , Angioedema/classificação , Angioedema/etiologia , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Árvores de Decisões , Humanos , Cininas/fisiologiaRESUMO
BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1Inh) associated with the c.983C>A and c.983C>G mutations of the F12 gene (FXII-HAE) is a rare condition, and presents with highly variable clinical expression. On the basis of data gathered from a large carrier cohort, we assessed the modifiers affecting the clinical phenotype. METHODS: We analyzed clinical and biological data recorded from 118 mutation carriers (80 symptomatic and 38 asymptomatic), 58 noncarrier relatives from 40 families, and 200 healthy donors. Disease severity was scored in relation to frequency and location of edema, as well as age at disease onset. To predict FXII-HAE disease severity, we analyzed the biological phenotype [C1Inh, C4, spontaneous amidase, angiotensin-I-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N/M (CPN)] by means of logistic regression (Akaike information criterion) and odds ratio (OR). RESULTS: Meaningful variables contributed to FXII-HAE, with the kinin catabolism enzymes ACE and CPN exhibiting a significant inverse relationship with disease severity (OR = 0.36, 95% CI 0.23-0.59, P < 0.001; OR = 0.58, 95% CI 0.36-0.91, P < 0.05, respectively). CPN activities were 37.5 (28.5-41.3) nmol/ml/min and 38.5 (32.8-45.6) for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 37.9 (30.5-43.7) nmol/ml/min for noncarriers. Angiotensin-I-converting enzyme activities were 58 (44-76) and 49 (35-59) nmol/ml/min for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 56 (49-66) nmol/ml/min for noncarriers. CONCLUSIONS: The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency.
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Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/genética , Fator XII/genética , Mutação , Fenótipo , Alelos , Angioedemas Hereditários/metabolismo , Estudos de Casos e Controles , Proteínas Inativadoras do Complemento 1/metabolismo , Proteína Inibidora do Complemento C1 , Éxons , Feminino , Heterozigoto , Humanos , Masculino , Razão de Chances , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The extraction of DNA from skeletal remains is a major step in archeological or forensic contexts. However, diagenesis of mineralized tissues often compromises this task although bones and teeth may represent preservation niches allowing DNA to persist over a wide timescale. This exceptional persistence is not only explained on the basis of complex organo-mineral interactions through DNA adsorption on apatite crystals composing the mineral part of bones and teeth but is also linked to environmental factors such as low temperatures and/or a dry environment. The preservation of the apatite phase itself, as an adsorption substrate, is another crucial factor susceptible to significantly impact the retrieval of DNA. With the view to bring physicochemical evidence of the preservation or alteration of diagenetic biominerals, we developed here an analytical approach on various skeletal specimens (ranging from ancient archeological samples to recent forensic specimens), allowing us to highlight several diagenetic indices so as to better apprehend the complexity of bone diagenesis. Based on complementary techniques (X-ray diffraction (XRD), Fourier transform infrared (FTIR), calcium and phosphate titrations, SEM-EDX, and gravimetry), we have identified specific indices that allow differentiating 11 biological samples, primarily according to the crystallinity and maturation state of the apatite phase. A good correlation was found between FTIR results from the analysis of the v3(PO4) and v4(PO4) vibrational domains and XRD-based crystallinity features. A maximal amount of information has been sought from this analytical approach, by way of optimized posttreatment of the data (spectral subtraction and enhancement of curve-fitting parameters). The good overall agreement found between all techniques leads to a rather complete picture of the diagenetic changes undergone by these 11 skeletal specimens. Although the heterogeneity and scarcity of the studied samples did not allow us to seek direct correlations with DNA persistence, the physicochemical parameters described in this work permit a fine differentiation of key properties of apatite crystals among post mortem samples. As a perspective, this analytical approach could be extended to more numerous sets of specimens so as to draw statistical relationships between mineral and molecular conservation.
Assuntos
Osso e Ossos/química , Cálcio/análise , Impressões Digitais de DNA/métodos , Fosfatos/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Dente/química , Difração de Raios X/métodos , Idoso de 80 Anos ou mais , Antropologia Física/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Aminopeptidases/deficiência , Angioedema/induzido quimicamente , Angioedema/enzimologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Bradicinina/metabolismo , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Doença Iatrogênica , Lisinopril/efeitos adversos , Lisina Carboxipeptidase/deficiência , Peptidil Dipeptidase A/deficiência , Pirazinas/efeitos adversos , Triazóis/efeitos adversos , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Angioedema/diagnóstico , Regulação para Baixo , Interações Medicamentosas , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Fatores de Risco , Fosfato de Sitagliptina , Fatores de TempoRESUMO
BACKGROUND: Hereditary C1-inhibitor (C1-Inh) deficiency is associated with 'bradykinin-mediated angio-oedema' (BK-AO) and is believed not to be associated with urticaria. Acquired AO has been related to oestrogen contraceptives. OBJECTIVE: To demonstrate that AO precipitated by oestrogens and characterized by nonfunctional C1-Inh is mediated by BK and to evaluate the occurrence of urticaria in these patients. METHODS: A retrospective evaluation of patients referred for AO related to oestrogen was undertaken. Circulating C1-Inh, high molecular weight kininogen (HK) and enzymes involved in the metabolism of bradykinin were investigated. RESULTS: Fifteen patients were included. HK cleavage concurrent to oestrogen intake was demonstrated in 10 patients with available plasma. Eight patients reported recurrent or chronic urticaria. Discontinuation of the contraceptive resulted in a return to native C1-Inh and HK in all cases studied and to normal kininogenase activity in all but one. The clinical manifestations completely disappeared in 6 patients and improved in 7 after the withdrawal of oestrogen. CONCLUSION: Patients display extensive cleavage of HK in the plasma, which supports that AO precipitated by oestrogen contraception is BK-mediated. Recurrent urticaria may have been underestimated in this context. The presence of recurrent urticaria should not systematically rule out the diagnosis of BK-AO when the history is suggestive.
Assuntos
Angioedema/induzido quimicamente , Bradicinina/metabolismo , Proteína Inibidora do Complemento C1/metabolismo , Anticoncepcionais Orais Hormonais/efeitos adversos , Estrogênios/efeitos adversos , Cininogênio de Alto Peso Molecular/sangue , Urticária/induzido quimicamente , Angioedema/sangue , Diagnóstico Diferencial , Feminino , Humanos , Estudos Retrospectivos , Urticária/sangueRESUMO
The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 µm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 µm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 µm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work.
Assuntos
Meio Ambiente Extraterreno , Marte , Calibragem , Meio Ambiente Extraterreno/química , Minerais/análise , Análise Espectral Raman/métodosRESUMO
BACKGROUND: Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype-phenotype relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of exon 2 has been reported to be associated with a more severe phenotype. We aimed to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and investigate the possible disease-aggravating effect of the c.-21T>C polymorphism. METHODS: Hereditary angioedema was diagnosed based on clinical features and C1 inhibitor deficiency. A general severity score ranging from 0 to 10 was developed based on age at disease onset, clinical manifestations and treatment experiences. SERPING1 gene investigation was performed by exon sequencing followed by multiplex ligation-dependent probe amplification genomic rearrangement analysis in all known Danish HAE families. RESULTS: Fifty-nine patients with HAE from 26 families were included in this study. The mean disease severity score was 7.12 [1-10], and the mean C1 inhibitor function was 26% [20-46%]. The sensitivity of the mutational screening was 96%, and 13 new mutations were found in this Danish patient cohort. Nine patients (15%) carried the c.-21T>C polymorphism, but they didn't have a more severe phenotype. CONCLUSION: Thirteen new mutations were identified in the Danish HAE population. No correlation between the c.-21T>C polymorphism, the biochemical values of C1 inhibitor function and the clinical severity score was found.
Assuntos
Angioedemas Hereditários/genética , Angioedemas Hereditários/fisiopatologia , Proteína Inibidora do Complemento C1/genética , Análise Mutacional de DNA , Adolescente , Adulto , Idoso , Angioedemas Hereditários/epidemiologia , Criança , Pré-Escolar , Dinamarca/epidemiologia , Família , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Polimorfismo Genético , Índice de Gravidade de Doença , Adulto JovemRESUMO
We have previously found that a Tyr residue was critical for the interaction of peptides with the Kd molecule, and therefore may be acting as an anchor residue. In the present report we show that it is possible to convert a self peptide sequence into a Kd-restricted neo-antigen by a single Tyr substitution at position 2 of the peptide. This supports the idea that Tyr is a critical element in the binding motif of Kd-restricted peptides and is a finding that could also prove useful for vaccine development.
Assuntos
Antígenos H-2/imunologia , Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Relação Estrutura-Atividade , Linfócitos T Citotóxicos/imunologia , TirosinaRESUMO
BACKGROUND: Hereditary angio-oedema (HAE) has been associated with C1inhibitor deficiency. The first cases of type III HAE were described in patients with normal C1Inh antigenic protein level and function and normal C4 levels in 2000. This finding has been reported mostly in women with a family history and may be influenced by exogenous oestrogen exposure. OBJECTIVES: The purpose of this article is to describe the clinical, biological and genetic characteristics of a French population suffering from type III HAE. PATIENTS AND METHODS: We conducted a retrospective analysis of angio-oedema (AE) cases seen in the National Reference Centre of AE between 2000 and 2009. RESULTS: We found 26 patients (from 15 unrelated families) with type III HAE. All but four were women and presented with typical AE attacks, exacerbated by pregnancy or oral contraceptives containing oestrogens (OC). We also found that 54.5% of women were worsened with oestrogen and 23% were oestrogen dependent. All patients improved on long-term prophylactic tranexamic acid treatment; some acute attacks improved with C1Inh concentrate infusion. All of the patients had normal C1Inh and C4 levels. C1Inh function was also normal, except in women receiving OC or during a pregnancy: transient, moderately low levels (32-74% of the normal range) were found in 18 patients tested (67%). No SERPING1 gene mutation was found. Six patients from three unrelated families were heterozygous for an F12 gene variant. CONCLUSION: Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence.
Assuntos
Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/epidemiologia , Estudos de Coortes , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Estrogênios/farmacologia , Fator XII/genética , Família , Feminino , França , Variação Genética , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêuticoRESUMO
SuperCam is a highly integrated remote-sensing instrumental suite for NASA's Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system.
RESUMO
Viruses require viral and cellular chaperones during their life cycle and interactions of these molecules with the immune system are probable during the infection. Thus, an anti-chaperone antibody response has been firstly investigated in hepatitis C patients in this paper. A HepG2-lysate antigen (90, 79, 72, 70, 62, 54 and 48 kDa) was assayed in sera from 59 (19F/40M) chronic hepatitis C patients without cirrhosis before therapy. Forty of them were positive for anti-HepG2 lysate antigen antibodies and this test may evaluate biological autoimmunity. Hsp70.1, Hsp90 and calreticulin levels were significantly higher in this antigen than in a control HepG2 antigen. Secondly, Hsp70.1 was identified as Hsp 70 kDa protein-1 by proteomic analysis and studied as a possible antibody target. Fourteen out of 59 patients were positive for anti-Hsp70.1 antibodies that were inversely correlated with alanine aminotransferase levels, the Metavir activity index and viraemia. Finally, for comparative purposes, 50 sera from systemic lupus erythematosus (SLE) patients have been tested: eight and 41 of them were positive for anti-Hsp70.1 and anti-HepG2 lysate antigen antibodies, respectively. Therefore, anti-Hsp70.1 autoantibodies may be produced and can partially lead to biological autoimmunity in chronic hepatitis C patients.
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Autoanticorpos/imunologia , Autoimunidade , Transportador de Glucose Tipo 1/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Hepatite C Crônica/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Linhagem Celular , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/imunologia , Curva ROC , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
INTRODUCTION: Moya-Moya angiopathy is a neurovascular disease that predisposes to ischemic or hemorrhagic strokes. It is generated by a steno-occlusion of the terminal portion of the internal carotid arteries, which induces the development of abnormal neovessels in the deep regions of the brain. Some pathologies such as sickle cell disease, Down syndrome or Graves' disease may be associated with Moya-Moya angiopathy. These syndromic forms harbor several differences compared with idiopathic Moya-Moya disease. CASE REPORT: We report the case of a young patient who presented with a syndromic form of Moya-Moya angiopathy after cranial radiation therapy for an optic glioma associated with type 1 neurofibromatosis treated by combined revascularization. We discuss the particularities of syndromic forms, in their presentation and management based on a review of the literature. CONCLUSION: Many diseases can be associated with Moya-Moya syndrome. Symptomatic patients should undergo surgery, but the risk of postoperative complications appears to be greater than that encountered in patients with non-syndromic Moya-Moya angiopathy.
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Irradiação Craniana/efeitos adversos , Doença de Moyamoya/cirurgia , Glioma do Nervo Óptico/radioterapia , Hemorragia Cerebral/diagnóstico por imagem , Revascularização Cerebral , Pré-Escolar , Feminino , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/etiologia , Neurofibromatose 1/complicações , Glioma do Nervo Óptico/etiologia , Síndrome , Adulto JovemAssuntos
Angioedema/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Bradicinina/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Doenças da Laringe/tratamento farmacológico , Idoso , Angioedema/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Doenças da Laringe/induzido quimicamente , Masculino , Perindopril/efeitos adversos , Pirazinas/efeitos adversos , Fosfato de Sitagliptina , Resultado do Tratamento , Triazóis/efeitos adversosAssuntos
Angioedema/tratamento farmacológico , Bradicinina , Ácido Tranexâmico/administração & dosagem , Adolescente , Adulto , Idoso , Angioedema/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
At inflammatory sites, before their processing, antigens are exposed to oxygen free radicals released by activated cells. The effect of hydroxyl radicals (OH.) on the structure of a protein antigen, tetanus toxin (TT) was investigated, as well as the consequences on processing and presentation. A chemical system composed of Fe-EDTA, ascorbate and H2O2 was used to produce physiological amounts of OH. radicals. TT exposed to OH. radicals presented a marked decrease of its intrinsic fluorescence with a concomitant increase of the content of bityrosine, but no fragmentation of the protein was detected by SDS-PAGE. Processing of the modified TT was analysed, by incubating TT at acidic pH with fractions enriched in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL). Proteolysis of OH.-treated TT was less important than proteolysis of native TT, especially upon prolonged incubations. Oxidized TT presented by LCL cells induced a greater proliferation of three different TT specific T cell clones, compared to native TT. When proteolytic digests of TT were presented by fixed LCL cells to a homologous T cell line, the proliferative response obtained in the presence of digests of OH.-treated TT was sustained, even in the case of prolonged proteolysis, whereas the response to digests of native TT fell rapidly. The relative resistance of OH.-treated TT to proteolysis appears thus responsible for its greater presentation to specific T cells, probably by protecting epitopes.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Linfócitos B/imunologia , Radical Hidroxila/farmacologia , Fragmentos de Peptídeos/imunologia , Toxina Tetânica/imunologia , Toxina Tetânica/metabolismo , Animais , Células Cultivadas , Células Clonais/imunologia , Endopeptidases/metabolismo , Humanos , Ativação Linfocitária/efeitos dos fármacos , Oxirredução , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/farmacologia , Espectrometria de Fluorescência , Frações Subcelulares/metabolismo , Linfócitos T/imunologia , Toxina Tetânica/farmacologia , Tirosina/análogos & derivados , Tirosina/análiseRESUMO
INTRODUCTION: Antimitochondrial type M5 antibodies (AMA-M5) are among the immunological abnormalities associated with Sneddon syndrome. CASE: A 45 year-old woman, hospitalized for diplopia and with a 20-year history of obstetrical accidents, internuclear ophthalmoplegia and livedo, was diagnosed with Sneddon syndrome associated with primary antiphospholipid syndrome (APS) aggravated by the presence of AMA-M5. DISCUSSION: AMA-M5 are immunological markers of APS to the same extent as antiphospholipid antibodies. This case demonstrates the interest of screening for AMA-M5 in cases of strong clinical suspicion of APS when the anticoagulant lupus test is normal and no anti-cardiolipin, anti-b2 glycoprotein I or antiprothrombin antibodies are found.
Assuntos
Síndrome Antifosfolipídica/complicações , Autoanticorpos/imunologia , Mitocôndrias/imunologia , Síndrome de Sneddon/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Sneddon/diagnósticoRESUMO
Both NS3 protein (1007-1657) and its protease moiety (NS3p, 1027-1207) were able to interact in vitro with C1 Inhibitor (C1Inh) to give a 95-kDa Mr C1Inh cleavage product similar to that obtained upon proteolysis by complement protease C1s. High-Mr reaction products were also detected after incubation of C1Inh with NS3 but not with NS3p; they correspond to ester-bonded complexes from their hydroxylamine lability. Similar reactivity of NS3 was observed upon incubation with alpha2-antiplasmin. Serpin cleavage was prevented by treatment of NS3 with synthetic serine protease inhibitors. This interaction between viral NS3 and host serpins suggests that NS3 is likely to be controlled by infected cell protease inhibitors.