RESUMO
Acute vascular rejection (AVR) is characterized by immune-mediated vascular injury and heightened endothelial cell (EC) apoptosis. We reported previously that apoptotic ECs release a bioactive C-terminal fragment of perlecan referred to as LG3. Here, we tested the possibility that LG3 behaves as a neoantigen, fuelling the production of anti-LG3 antibodies of potential importance in regulating allograft vascular injury. We performed a case-control study in which we compared anti-LG3 IgG titers in kidney transplant recipients with AVR (n=15) versus those with acute tubulo-interstitial rejection (ATIR) (n=15) or stable graft function (n=30). Patients who experienced AVR had elevated anti-LG3 titers pre and posttransplantation compared to subjects with ATIR or stable graft function (p<0.05 for both mediators). Elevated pretransplant anti-LG3 titers (OR: 4.62, 95% CI: 1.08-19.72) and pretransplant donor-specific antibodies (DSA) (OR 4.79, 95% CI: 1.03-22.19) were both independently associated with AVR. To address the functional role of anti-LG3 antibodies in AVR, we turned to passive transfer of anti-LG3 antibodies in an animal model of vascular rejection based on orthotopic aortic transplantation between fully MHC-mismatched mice. Neointima formation, C4d deposition and allograft inflammation were significantly increased in recipients of an ischemic aortic allograft passively transferred with anti-LG3 antibodies. Collectively, these data identify anti-LG3 antibodies as novel accelerators of immune-mediated vascular injury and obliterative remodeling.
Assuntos
Rejeição de Enxerto/imunologia , Proteoglicanas de Heparan Sulfato/imunologia , Imunoglobulina G/sangue , Doenças Vasculares/imunologia , Adulto , Animais , Antígenos/imunologia , Aorta/patologia , Apoptose , Estudos de Casos e Controles , Células Endoteliais/patologia , Feminino , Rejeição de Enxerto/sangue , Humanos , Imunização Passiva , Imunoglobulina G/imunologia , Inflamação/patologia , Rim/irrigação sanguínea , Rim/patologia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Estudos Retrospectivos , Doenças Vasculares/sangueRESUMO
OBJECTIVES: To compare the feasibility of two transabdominal approaches for performing first-trimester uterine artery (UtA) Doppler and to evaluate the correlation with pulsatility index (PI) in the second trimester. METHODS: This was a prospective longitudinal Doppler study of the uterine arteries at 11-13 and 21-22 weeks' gestation. Transabdominal ultrasound and color Doppler were used to measure the UtA-PI of the ascending branch of the uterine artery at the level of the internal cervical os (Site A) and at the level of the apparent crossover with the external iliac artery (Site B) at 11-13 weeks, and at Site B only at 21-22 weeks. In all cases the measured left and right PI were converted to a multiple of the median (MoM) for gestational age, and the intercorrelation between the measurements at different sites and gestational ages was calculated using non-parametric analysis (Spearman's rank correlation). RESULTS: Satisfactory measurements were obtained at 11-13 weeks from both uterine arteries in all 81 women at Site A and in 50 (62%; 95% CI, 50-72%) at Site B (P < 0.01). Measurements were obtained at Site B at 21-22 weeks in all cases. In the 50 cases with measurements from both sites at 11-13 weeks, the correlation of PI-MoMs between Sites A and B at 11-13 weeks was only moderate (ρ = 0.61). The correlation between first-trimester UtA-PI MoMs at Site A and second-trimester UtA-PI MoMs was stronger than that between first-trimester UtA-PI MoMs at Site B and second-trimester UtA-PI MoMs (ρ = 0.73 vs ρ = 0.47, P < 0.01). CONCLUSION: Evaluation of UtA-PI at 11-13 weeks can be achieved at the level of the internal cervical os in a greater proportion of women than at the level of the apparent crossover with the external iliac vessels, and the measurements obtained correlate better with second-trimester UtA-PI.
Assuntos
Fluxo Pulsátil/fisiologia , Ultrassonografia Doppler em Cores/métodos , Artéria Uterina/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Estudos Longitudinais , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos ProspectivosRESUMO
To obtain more precise data on pulmonary doses in preparation for total body irradiation, the lung density of patients was systematically analyzed in treatment positions using data obtained by computed tomography (CT). With the patient supine, the lung density was not significantly different for the right and left lungs. In contrast, considerable differences were noted between the two lungs in lateral decubitus positions owing to variations in ventilation and perfusion. The relative electron density of lung was also found to decrease with age, dropping to pe = 0.160 at 71 years.
Assuntos
Absorciometria de Fóton , Pulmão/diagnóstico por imagem , Postura , Irradiação Corporal Total , Humanos , Gravidade Específica , Tomografia Computadorizada por Raios XRESUMO
A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Janni's tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.
Assuntos
Radiometria/métodos , Calibragem , Calorimetria , Íons , Doses de Radiação , Radiometria/instrumentaçãoRESUMO
The authors present the summary of a workshop of a group of radiation oncologists and radiation physicists on three dimensional treatment planning and conformal radiation therapy with multileaf collimator. It appears that this technic must be considered as experimental and that it cannot be promoted in all radiotherapy departments without scientific and clinical evaluation.
Assuntos
Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Alta Energia , Estudos de Avaliação como Assunto , Humanos , Aceleradores de Partículas , Controle de Qualidade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/economia , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Alta Energia/economia , Radioterapia de Alta Energia/instrumentação , Radioterapia de Alta Energia/métodosRESUMO
OBJECTIVE: To estimate the correlation between first-trimester placental volume, birth weight, small-for-gestational-age (SGA), and preeclampsia. METHODS: A prospective study of women with singleton pregnancy at 11-13 weeks of gestation was conducted. First-trimester placental volume was measured using three-dimensional ultrasound and reported as multiple of median (MoM) for gestational age. Participants were followed until delivery where birth weight, placental weight, and occurrence of preeclampsia were collected. Non-parametric analyses were performed. RESULTS: We reached a complete follow-up for 543 eligible women. First-trimester placental volume was significantly correlated with birth weight (correlation coefficient: 0.18; p < 0.0001) and placental weight (cc: 0.22; p < 0.0001) adjusted for gestational age. First-trimester placental volume was smaller in women who delivered SGA neonates (median MoM: 0.79; interquartile range: 0.62-1.00; p < 0.001) and greater in women who delivered large-for-gestational-age neonates (median MoM: 1.13; 0.95-1.49; p < 0.001) when compared to women with neonates between the 10th and 90th percentile (median MoM: 1.00; 0.81-1.25). First-trimester placental volume was not associated with the risk of preeclampsia (cc: 0.01; p = 0.87). CONCLUSION: First-trimester placental volume is strongly associated with fetal and placental growth. However, we did not observe a correlation between placental volume and the risk of preeclampsia.
Assuntos
Placenta/anatomia & histologia , Primeiro Trimestre da Gravidez , Adulto , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Tamanho do Órgão , Pré-Eclâmpsia , Gravidez , Estudos Prospectivos , Ultrassonografia Pré-NatalRESUMO
The apoptotic program incorporates a paracrine component of importance in fostering tissue repair at sites of apoptotic cell deletion. As this paracrine pathway likely bears special importance in maladaptive intercellular communication leading to vascular remodeling, we aimed at further defining the mediators produced by apoptotic endothelial cells (EC), using comparative and functional proteomics. Apoptotic EC were found to release nanovesicles displaying ultrastructural characteristics, protein markers and functional activity that differed from apoptotic blebs. Tumor susceptibility gene 101 and translationally controlled tumor protein (TCTP) were identified in nanovesicle fractions purified from medium conditioned by apoptotic EC and absent from purified apoptotic blebs. Immunogold labeling identified TCTP on the surface of nanovesicles purified from medium conditioned by apoptotic EC and within multivesicular blebs in apoptotic EC. These nanovesicles induced an extracellular signal-regulated kinases 1/2 (ERK 1/2)-dependent antiapoptotic phenotype in vascular smooth muscle cells (VSMC), whereas apoptotic blebs did not display antiapoptotic activity on VSMC. Caspase-3 biochemical inhibition and caspase-3 RNA interference in EC submitted to a proapoptotic stimulus inhibited the release of nanovesicles. Also, TCTP siRNAs in EC attenuated the antiapoptotic activity of purified nanovesicles on VSMC. Collectively, these results identify TCTP-bearing nanovesicles as a novel component of the paracrine apoptotic program of potential importance in vascular repair.
Assuntos
Apoptose , Biomarcadores Tumorais/metabolismo , Caspase 3/metabolismo , Comunicação Celular , Animais , Células Endoteliais/citologia , Células Endoteliais/enzimologia , Células Endoteliais/ultraestrutura , Ativação Enzimática , Exossomos/ultraestrutura , Humanos , Nanoestruturas/ultraestrutura , Transporte Proteico , Ratos , Soro , Proteína Tumoral 1 Controlada por Tradução , Veias Umbilicais/citologiaRESUMO
An outbreak of hepatitis A in a rural river-island community was found to be associated with consumption of contaminated well water. Specimens from case-patients, the implicated well, and a cesspool suspected to be the source of contamination were all positive for hepatitis A virus (HAV) RNA by immunocapture reverse-transcription polymerase chain reaction. All isolates were identical over about 400 bases from two capsid-encoding regions of the genome, identifying the chain of transmission. Other wells up to 60 m from the cesspool also contained HAV RNA. In addition, HAV RNA was detected in the contamination source well 6 months after the initial contamination, when fecal coliform bacteria were no longer present. These findings demonstrate the utility of viral detection techniques to evaluate contaminated ground water.