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Some years ago, the consensus was that asteroid (16) Psyche was almost entirely metal. New data on density, radar properties, and spectral signatures indicate that the asteroid is something perhaps even more enigmatic: a mixed metal and silicate world. Here we combine observations of Psyche with data from meteorites and models for planetesimal formation to produce the best current hypotheses for Psyche's properties and provenance. Psyche's bulk density appears to be between 3,400 and 4,100 kg m-3. Psyche is thus predicted to have between ~30 and ~60 vol% metal, with the remainder likely low-iron silicate rock and not more than ~20% porosity. Though their density is similar, mesosiderites are an unlikely analog to bulk Psyche because mesosiderites have far more iron-rich silicates than Psyche appears to have. CB chondrites match both Psyche's density and spectral properties, as can some pallasites, although typical pallasitic olivine contains too much iron to be consistent with the reflectance spectra. Final answers, as well as resolution of contradictions in the data set of Psyche physical properties, for example, the thermal inertia measurements, may not be resolved until the NASA Psyche mission arrives in orbit at the asteroid. Despite the range of compositions and formation processes for Psyche allowed by the current data, the science payload of the Psyche mission (magnetometers, multispectral imagers, neutron spectrometer, and a gamma-ray spectrometer) will produce data sets that distinguish among the models.
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The present study examined and compared the effects of 2 analogues of cognitive treatments-cognitive defusion and cognitive reappraisal-on symbolically generalized avoidance established using a basic behavioral laboratory paradigm. This back-translation design contributes to the development and validation of principle-based definitions of the applied constructs of defusion and reappraisal. Eighty-eight participants first underwent basic laboratory procedures designed to establish symbolically generalized avoidance in response to an arbitrary stimulus (a nonsense word). Participants were then randomized to defusion, reappraisal, or control conditions. The response variables were (a) equivalence responding-indicative of the trained relational network and analogous to the cognitive content responsible for symbolic generalization-and (b) avoidance-the behavioral impact of symbolic generalization. A between-groups analysis revealed that defusion and reappraisal significantly increased the odds of nonavoidance responding. Discrete-time survival mediation analyses provided preliminary support for the classification of defusion as a functional context intervention and reappraisal as a relational context intervention.
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Aprendizagem da Esquiva , Generalização Psicológica , Adolescente , Adulto , Condicionamento Operante , Feminino , Humanos , Masculino , Reforço Psicológico , Recompensa , Adulto JovemRESUMO
OBJECTIVE: To evaluate the relationship of telomere length to the prevalence and incidence of hand osteoarthritis in a longitudinal cohort. DESIGN: We conducted a cross-sectional and longitudinal analysis of data from a subset of participants in the Osteoarthritis Initiative (OAI) recruited between February 2004 and May 2006. 274 individuals were eligible for the study based on availability of both baseline and 48-month hand radiographs and peripheral blood leucocyte telomere length data. Mean telomere length of peripheral blood leukocytes (PBL)s from the DNA samples was determined using a validated quantitative polymerase chain reaction (PCR)-based assay, and hand radiographs were analyzed and graded using the Kellgren-Lawrence scale. RESULTS: In joint -level analyses, prevalent Interphalangeal Joint Osteoarthritis (IPJOA) was significantly associated with PBL telomere length in the baseline sample in unadjusted analyses (RR = 2.84; 95% CI:0.87-9.29) or in models adjusted for age, sex, and body mass index (aRR = 1.10; 95% CI: 0.96-1.27). The association in crude and adjusted analyses appeared slightly stronger with incident IPJOA, especially in the subset with normal hands at baseline (aRR = 1.62; 95% CI: 1.02-2.57). PBL telomere length was also associated with prevalent HOA at baseline (significant in unadjusted analysis: RR = 1.22; 95% CI 1.06-1.42), but not after adjusting for covariates: aRR = 1.12; 95% CI: 0.96-1.30). The magnitude of association was stronger for incident HOA, especially incident symptomatic HOA (aRR = 1.53; 95% CI: 1.09-2.15). CONCLUSIONS: In summary, the results of this exploratory analysis are confirmatory of previous work showing a cross-sectional relationship between telomere length and HOA and add to the field by demonstrating an even stronger association with incident IPJOA, both radiographic and symptomatic.
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Articulação da Mão/diagnóstico por imagem , Leucócitos/fisiologia , Osteoartrite/genética , Encurtamento do Telômero/fisiologia , Idoso , Estudos Transversais , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoartrite/sangue , Osteoartrite/diagnóstico por imagem , Osteoartrite/epidemiologia , Prevalência , Telômero/fisiologia , Estados Unidos/epidemiologiaRESUMO
PURPOSE: 3D Magnetic resonance imaging (MRI) scans are generally used for quantitative cartilage measurements in knee osteoarthritis. However, a great deal of MRI data is from 2D scans, often thought to be unsuitable for quantitative cartilage assessment. The goal of our study was to demonstrate that mLACS, a modified version of the Local Area Cartilage Segmentation (LACS) method, could be used to measure cartilage volume on 2D MRI images. METHODS: We studied 301 randomly selected subjects from the OA Biomarkers Consortium FNIH Study, a nested case-control study within the Osteoarthritis Initiative (OAI). The study comprised four subgroups based on radiographic and pain progression. We compared mLACS applied to 2D TSE scans to LACS on 3D DESS data. The Pearson's correlation coefficient was used to establish agreement between LACS and mLACS, standardized response means (SRMs) for responsiveness, and intra-class correlation coefficients (ICCs) to measure reader precision. Logistic regression in a case/control analysis was used to compare the clinical validity between the two methods. RESULTS: We found R2 = 0.76 for the correlation between LACS and mLACs. For LACS, the responsiveness was SRM = 0.49 compared to 0.39 for mLACS. The odds ratios (OR) for the primary case/control analyses were 1.62 for LACS and 1.78 for mLACS. The intra and inter reader reproducibility values for mLACS were ICC = 0.90 and 0.86, respectively. CONCLUSION: This study has demonstrated that a reproducible, responsive, and clinically valid quantitative measurement of cartilage volume can be made using 2D TSE scans with a modest loss of responsiveness compared to 3D scans.
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Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Idoso , California , Estudos de Casos e Controles , Progressão da Doença , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Medição de RiscoRESUMO
OBJECTIVE: Large studies of knee osteoarthritis (KOA) require well-characterized efficient methods to assess progression. We previously developed the local-area cartilage segmentation (LACS) software method, to measure cartilage volume on magnetic resonance imaging (MRI) scans. The present study further validates this method in a larger patient cohort and assesses predictive validity in a case-control study. METHOD: The OA Biomarkers Consortium FNIH Project, a case-control study of KOA progression nested within the Osteoarthritis Initiative (OAI), includes 600 subjects in four subgroups based on radiographic and pain progression. Our software tool measured change in medial femoral cartilage volume in a central weight-bearing region. Different sized regions of cartilage were assessed to explore their sensitivity to change. The readings were performed on MRI scans at the baseline and 24-month visits. We used standardized response means (SRMs) for responsiveness and logistic regression for predictive validity. RESULTS: Cartilage volume change was associated strongly with radiographic progression (odds ratios (OR) = 4.66; 95% confidence intervals (CI) = 2.85-7.62). OR were significant but of lesser magnitude for the combined radiographic and pain progression outcome (OR = 1.70; 95% CI = 1.40-2.07). For the full 600 subjects, theSRM was -0.51 for the largest segmented area. Smaller areas of cartilage segmentation were also able to predict the case-control status. The average reader time for the largest area was less than 20 min per scan. Smaller areas could be assessed with less reader time. CONCLUSION: We demonstrated that the LACS method is fast, responsive, and associated with radiographic and pain progression, and is appropriate for existing and future large studies of KOA.
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Cartilagem Articular/patologia , Osteoartrite do Joelho/patologia , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de RiscoRESUMO
The Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4) is a 22-item five-factor measure that assesses thin- and muscular-ideal internalization as well as appearance-related pressures from peers, family, and media. The scale has been validated in Western cultures, but has not yet been examined in Eastern samples. Two studies were conducted to examine the psychometric properties of the SATAQ-4 among 946 Japanese adolescent girls. In Study 1, exploratory factor analysis of the SATAQ-4 indicated that the five-factor structure was largely replicated with the exception of two cross-loading items. In Study 2, confirmatory factor analysis indicated good fit for the full 22-item and reduced 20-item versions of the measure. SATAQ-4 subscales exhibited good internal consistency and were correlated in the expected direction with experiences of appearance teasing, strategies to lose and/or gain weight, and drive for muscularity. Overall, results support the reliability and validity of the SATAQ-4 among Japanese adolescent girls.
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Atitude , Imagem Corporal/psicologia , Psicometria/instrumentação , Inquéritos e Questionários/normas , Adolescente , Feminino , Humanos , Japão/etnologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Magnetic resonance imaging (MRI) is a widely used imaging modality for studies of knee osteoarthritis (OA). Compared to radiography, MRI offers exceptional soft tissue imaging and true three-dimensional (3D) visualization. However, MRI is expensive both due to the cost of acquisition and evaluation of the images. The goal of our study is to develop a new method to address the cost of MRI by combining innovative acquisition methods and automated post-processing software. METHODS: Ten healthy volunteers were scanned with three different MRI protocols: A standard 3D dual-echo steady state (DESS) pulse sequence, an accelerated DESS (DESSAcc), acquired at approximately half the time compared to DESS, and a multi-echo time DESS (DESSMTE), which is capable of producing measurements of T2 relaxation time. A software tool was used to measure cartilage volume. Accuracy was quantified by comparing DESS to DESSAcc and DESSMTE and precision was measured using repeat readings and acquisitions. T2 precision was determined using duplicate DESSMTE acquisitions. Intra-class correlation coefficients (ICCs), root-mean square standard deviation (RMSSD), and the coefficient of variation (CoV) were used to quantify accuracy and precision. RESULTS: The accuracies of DESSAcc and DESSMTE were CoV = 3.7% and CoV = 6.6% respectively, while precision was 3.8%, 3.0%, and 3.1% for DESS, DESSAcc and DESSMTE. T2 repositioning precision was 5.8%. CONCLUSION: The results demonstrate that accurate and precise quantification of cartilage volume is possible using a combination of substantially faster MRI acquisition and post-processing software. Precise measurements of cartilage T2 and volume can be made using the same acquisition.
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Osteoartrite do Joelho , Cartilagem Articular , Humanos , Articulação do Joelho , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , SoftwareRESUMO
This paper evaluates the biological regeneration of ferric Fe3+ solution during desulphurisation of gaseous streams. Hydrogen sulphide (H2S) is absorbed into aqueous ferric sulphate solution and oxidised to elemental sulphur, while ferric ions Fe3+ are reduced to ferrous ions Fe2+. During the industrial regeneration of Fe3+, nutrients and trace minerals usually provided in a laboratory setup are not present and this depletion of nutrients may have a negative impact on the bacteria responsible for ferrous iron oxidation and may probably affect the oxidation rate. In this study, the effect of nutrients and trace minerals on ferrous iron oxidation have been investigated and the results showed that the presence of nutrients and trace minerals affects the efficiency of bacterial Fe2+oxidation. The scanning electron microscopy analysis of the geotextile support material was also conducted and the results showed that the iron precipitate deposits appear to play a direct role on the bacterial biofilm formation.
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Fenômenos Fisiológicos Bacterianos , Biofilmes , Compostos Férricos/metabolismo , Compostos Ferrosos/metabolismo , Sulfeto de Hidrogênio/metabolismo , Enxofre/metabolismo , Microscopia Eletrônica de Varredura , OxirreduçãoRESUMO
Investigations were carried out to evaluate and quantify colonization of laboratory-scale drinking water biofilms by a chromosomally green fluorescent protein (gfp)-tagged strain of Salmonella Typhimurium. Gfp encodes the green fluorescent protein and thus allows in situ detection of undisturbed cells and is ideally suited for monitoring Salmonella in biofilms. The fate and persistence of non-typhoidal Salmonella in simulated drinking water biofilms was investigated. The ability of Salmonella to form biofilms in monoculture and the fate and persistence of Salmonella in a mixed aquatic biofilm was examined. In monoculture S. Typhimurium formed loosely structured biofilms. Salmonella colonized established multi-species drinking water biofilms within 24 hours, forming micro-colonies within the biofilm. S. Typhimurium was also released at high levels from the drinking water-associated biofilm into the water passing through the system. This indicated that Salmonella could enter into, survive and grow within, and be released from a drinking water biofilm. The ability of Salmonella to survive and persist in a drinking water biofilm, and be released at high levels into the flow for recolonization elsewhere, indicates the potential for a persistent health risk to consumers once a network becomes contaminated with this bacterium.
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Biofilmes/crescimento & desenvolvimento , Água Potável/microbiologia , Salmonella typhimurium/fisiologia , Proteínas de Fluorescência VerdeRESUMO
Mineral mining generates acidic, saline, metal-rich mine waters, often referred to as acid mine drainage (AMD). Treatment of AMD and recovering saleable products during the treatment process are a necessity since water is, especially in South Africa, a scarce commodity. The aim of the study presented here was to investigate the effect of zero valent iron (Fe(0)) on the biological removal of sulphate from AMD in batch reactors. The performance of the reactors was assessed by means of sulphate reduction, chemical oxygen demand (COD), volatile fatty acid (VFA) utilisation and volatile suspended solids (VSS) concentration. To this end, three batch reactors, A, B and C (volume 2.5 L), were operated similarly with the exception of the addition of grass cuttings and iron filings. Reactors A and B received twice as much grass (100 g) as C (50 g). Reactor A received no iron filings to act as a control, while reactors B and C received 50-g iron filings for the experimental duration. The results showed that Fe(0) appears to provide sustained sulphate removal when sufficient grass substrate is available. In reactors A and C, sulphate removal efficiency was higher when the COD concentration was lower due to utilisation. In reactor B, sulphate removal efficiency was accompanied by an accumulation of COD as hydrogen (H2) provided by the Fe(0) was utilised for sulphate reduction. Furthermore, these results showed the potential of Fe(0) to enhance the participation of microorganisms in sulphate reduction.
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Análise da Demanda Biológica de Oxigênio , Carbono/metabolismo , Celulose/metabolismo , Ferro/metabolismo , Reatores Biológicos , Celulose/química , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Ferro/química , Poaceae/química , África do Sul , Sulfatos/química , Eliminação de Resíduos LíquidosRESUMO
PURPOSE: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR imaging of the renal vasculature and to evaluate the diagnostic potential of various nonenhanced T1-weighted (T1w) sequences. MATERIALS AND METHODS: Twelve healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T, Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF) transmit/receive body coil. Subsequent to RF shimming, the following sequences were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR and CNR were measured in the aorta and both renal arteries. Qualitative analysis was performed with regard to vessel delineation (5-point scale: 5 = excellent to 1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact present to 1 = strong impairment). RESULTS: The inherently high signal intensity of the renal arterial vasculature in T1w imaging enabled moderate to excellent vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative analysis (SNR(mean) : 53.9; CNR(mean) : 28.0) demonstrated the superiority of TOF MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI demonstrated its potential for fast high quality imaging of the nonenhanced arterial vasculature, providing homogeneous hyperintense vessel signal. CONCLUSION: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear to be promising techniques for good quality nonenhanced renal artery assessment at 7 Tesla.
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Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Artéria Renal/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Although deficiency of the small leucine-rich proteoglycan decorin aggravates diabetic nephropathy in mice, the precise mechanisms of action are not fully understood. In the present study we used decorin-deficient mice (Dcn(-/-)) to further elucidate the molecular mechanisms involved in the protective action of decorin in diabetes. We discovered that streptozotocin-induced diabetes in Dcn(-/-) mice led to increased proteinuria associated with enhanced cyclin-dependent kinase inhibitor p27Kip1 in podocytes and tubular epithelial cells. Furthermore, lack of decorin increased the rate of apoptosis and caused overexpression of the IGF-IR in tubular epithelial cells of diabetic kidneys. In vitro experiments using human proximal renal epithelial cells showed that recombinant decorin was bound to the IGF-IR and protected against high glucose-mediated apoptosis. Furthermore, overexpression of TGFbeta1 and CTGF triggered by decorin deficiency resulted in enhanced accumulation of extracellular matrix in diabetic kidneys. Notably, diabetic Dcn(-/-) kidneys revealed marked upregulation of the proinflammatory proteoglycan biglycan and enhanced infiltration of mononuclear cells. Collectively, our results indicate that decorin is a protective agent during the development of diabetic nephropathy. Future therapeutic approaches that would either enhance the endogenous production of decorin or deliver recombinant decorin to the diseased kidney might improve the outcome of patients with diabetic nephropathy.
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Apoptose/fisiologia , Diabetes Mellitus/metabolismo , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Proteínas da Matriz Extracelular/deficiência , Monócitos/fisiologia , Proteoglicanas/deficiência , Animais , Northern Blotting , Western Blotting , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Decorina , Diabetes Mellitus/genética , Células Epiteliais/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Fibrose/metabolismo , Humanos , Rim/metabolismo , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos/fisiologia , Podócitos/metabolismo , Polissacarídeos/metabolismo , Proteinúria/metabolismo , Proteoglicanas/genética , Receptor IGF Tipo 1/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI. METHODS AND RESULTS: Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI. CONCLUSIONS: Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.
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Proteínas da Matriz Extracelular/metabolismo , Infarto do Miocárdio/metabolismo , Proteoglicanas/metabolismo , Remodelação Ventricular/fisiologia , Análise de Variância , Animais , Biglicano , Cicatriz , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/genética , Genótipo , Ruptura Cardíaca Pós-Infarto/metabolismo , Hemodinâmica , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Knockout , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Fenótipo , Proteoglicanas/deficiência , Proteoglicanas/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The biology of chemokines and their receptors have been linked to the development of chronic allograft damage. Effects of CCR1 antagonist BX 471 were studied in a Fischer to Lewis renal transplantation model at days 10, 21 and 42 after transplantation. BX 471 treatment did not effectively reduce signs of acute rejection at day 10 but significantly improved allograft function and morphology at day 21 posttransplantation. When therapy was initiated on day 21 after transplantation, glomerulosclerosis and tubulointerstitial fibrosis were significantly inhibited by day 42 posttransplantation. Parallel decrease in infiltrating and proliferating mononuclear cells (ED1, CD8 and Ki67) was observed in treated allografts. Expression of acute phase reactive and proinflammatory genes (HO-1, osteopontin) and molecules associated with fibrosis (PAI-1, TGF-beta1, biglycan) was downregulated at day 21; reduced collagen deposition was observed, parallel to a significant lower number of alpha-SMA+ interstitial myofibroblasts. In situ hybridization demonstrated that biglycan expression was reduced following CCR1 blockade in interstitium of treated allografts. CCR1 antagonism was found to inhibit CCL5-induced secretion of biglycan by macrophages in vitro. CCR1 blockade significantly inhibited development and progression of chronic allograft damage. CCR1 antagonists may represent a therapeutic option for chronic inflammation and fibrosis in renal grafts.
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Rejeição de Enxerto/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Transplante de Rim , Compostos de Fenilureia/uso terapêutico , Piperidinas/uso terapêutico , Receptores de Quimiocinas/antagonistas & inibidores , Animais , Biglicano , Progressão da Doença , Proteínas da Matriz Extracelular/antagonistas & inibidores , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Falência Renal Crônica/patologia , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Modelos Animais , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Proteoglicanas/antagonistas & inibidores , Proteoglicanas/genética , Proteoglicanas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Receptores CCR1 , Linfócitos T/efeitos dos fármacosRESUMO
AIMS/HYPOTHESIS: We quantified the glomerular expression of thrombospondin-1 (THBS1, also known as TSP-1), transforming growth factor beta 1 (TGFB1, also known as TGF-beta1) and connective tissue growth factor (CTGF) at each stage of diabetic nephropathy. We also examined the roles of THBS1 and CTGF in mediating high-glucose- and glycated-albumin-induced synthesis of the matrix protein, fibronectin, by mesangial cells. METHODS: THBS1, latent and active TGFB1, and CTGF, were detected by immunohistochemistry and in situ hybridisation in biopsies from 19 insulin-dependent diabetic patients with incipient, manifest and advanced diabetic nephropathy, and in 11 control kidneys. Findings were quantified by image analysis. Human mesangial cells were cultured with normal or high glucose, albumin or glycated albumin (Amadori product), +/-THBS1 or CTGF antisense oligonucleotides, or with peptide W, an inhibitor of TGFB1 bioactivation by THBS1. Proteins were measured by western blot analysis or ELISA. RESULTS: In glomeruli of normal kidneys, mRNA and protein levels for THBS1, latent-TGFB1 and CTGF were low. They were increased in the incipient stage of diabetic nephropathy, predominantly in mesangial areas, with further increases at later stages of the disease. Little or no active TGFB1 immunostaining was detected prior to manifest diabetic nephropathy. In contrast to high-glucose conditions, increases in fibronectin synthesis that were stimulated by glycated albumin were not dependent on THBS1 activation of latent TGFB1. However, increased fibronectin synthesis in both conditions required CTGF. CONCLUSIONS/INTERPRETATION: Increased glomerular expression of all three factors occurs from the earliest stage of diabetic nephropathy. In contrast to THBS1, CTGF is required for mesangial synthesis of fibronectin stimulated by high glucose or glycated albumin, and is thus a potential therapeutic target.
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Nefropatias Diabéticas/metabolismo , Mesângio Glomerular/metabolismo , Hiperglicemia/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto , Idoso , Western Blotting , Estudos de Casos e Controles , Fator de Crescimento do Tecido Conjuntivo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fibronectinas/genética , Fibronectinas/metabolismo , Regulação da Expressão Gênica , Mesângio Glomerular/patologia , Glucose/farmacologia , Glucose/fisiologia , Produtos Finais de Glicação Avançada , Humanos , Proteínas Imediatamente Precoces/genética , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , RNA Mensageiro/genética , Albumina Sérica/farmacologia , Trombospondina 1/genética , Fator de Crescimento Transformador beta/genética , Albumina Sérica GlicadaRESUMO
Practical applications of structured illumination microscopy (SIM) often suffer from various artefacts that result from imprecise instrumental hardware and certain bleaching properties of the sample. These artefacts can be observed as residual stripe patterns originating from the illumination grating. We investigated some significant causes of these artefacts and developed a correction approach that can be applied to images after acquisition. Most of the artefacts can be attributed to changes in illumination and detection intensities during acquisition. The proposed correction algorithm has been shown to be functional on noisy image data, and produces exceptional, artefact-free results in everyday laboratory work.
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Artefatos , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Actinas/ultraestrutura , Algoritmos , Sensibilidade e Especificidade , SoftwareRESUMO
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has been our choice operation for morbid obesity since 1994. Despite a long list of publications about the LAGB during recent years, the evidence with regard to long-term weight loss after LAGB has been rather sparse. The outcome of the first 100 patients and the total number of 984 LAGB procedures were evaluated. METHODS: 984 consecutive patients (82.5% female) underwent LAGB. Initial body weight was 132.2 +/- 23.9 SD kg and body mass index (BMI) was 46.8 +/- 7.2 kg/m(2). Mean age was 37.9 (18-65). Retrogastric placement was performed in 577 patients up to June 1998. Thereafter, the pars flaccida to perigastric (two-step technique) was used in the following 407 patients. RESULTS: Mortality and conversion rates were 0. Follow-up of the first 100 patients has been 97% and ranges in the following years between 95% and 100% (mean 97.2%). Median follow-up of the first 100 patients who were available for follow-up was 98.9 months (8.24 years). Median follow-up of all patients was 55.5 months (range 99-1). Early complications were 1 gastric perforation after previous hiatal surgery and 1 gastric slippage (band was removed). All complications were seen during the first 100 procedures. Late complications of the first 100 cases included 17 slippages requiring reinterventions during the following years; total rate of slippage decreased later to 3.7%. Mean excess weight loss was 59.3% after 8 years, if patients with band loss are excluded. BMI dropped from 46.8 to 32.3 kg/m(2). 5 patients of the first 100 LAGB had the band removed, followed by weight gain; 3 of the 5 patients underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) with successful weight loss after the redo-surgery. 14 patients were switched to a "banded" LRYGBP and 2 patients to a LRYGBP during 2001-2002. The quality of life indices were still improved in 82% of the first 100 patients. The percentages of good and excellent results were at the highest level at 2 years after LAGB (92%). CONCLUSIONS: LAGB is safe, with a lower complication rate than other bariatric operations. Reoperations can be performed laparoscopically with low morbidity and short hospitalizations. The LAGB seems to be the basic bariatric procedure, which can be switched laparoscopically to combined bariatric procedures if treatment fails. After the learning curve of the surgeon, results are markedly improved. On the basis of 8 years long-term follow-up, it is an effective procedure.
Assuntos
Gastroplastia/métodos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Gravidez/estatística & dados numéricos , Qualidade de Vida , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Gastroplastia/efeitos adversos , Alemanha , Humanos , Incidência , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico , Seleção de Pacientes , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Redução de PesoRESUMO
Decorin, a small multifunctional proteoglycan, has been shown to be causally involved in the formation of capillary-like structures and a decrease in apoptosis. Here we investigated signal transduction pathways mediating effects of decorin on endothelial cells (ECs). Addition of decorin led to a fourfold increase in phosphorylation of Akt/protein kinase B on Thr307 and a l.4-fold increase on Ser473 after 10 min, but this phosphorylation could not be blocked by preincubation with Ly29400 (10 micro M). Six hours after the addition of decorin, the synthesis of p21 and p27, two inhibitors of cyclin-dependent kinases, started and increased up to 18 h, while synthesis of cyclin A peaked at 12 h and decreased after 24 h below base level. Induction of dominan-negative Akt by a replication-deficient adenovirus blocked p21 and cyclin A synthesis, but had no effect on p27. Dominant-negative Akt also blocked the antiapoptotic effect of decorin on ECs, but induction of dominant-positive Akt could not rescue the cells from apoptosis. Thus, the matrix proteoglycan decorin is a signaling molecule in ECs that affects cell survival by Akt-dependent and -independent pathways.
Assuntos
Endotélio Vascular/fisiologia , Proteínas Serina-Treonina Quinases , Proteoglicanas/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Linhagem Celular , Decorina , Endotélio Vascular/efeitos dos fármacos , Proteínas da Matriz Extracelular , Cinética , Fosforilação , Fosfosserina/metabolismo , Fosfotreonina , Proteínas Proto-Oncogênicas c-akt , Fator de Crescimento Transformador beta/antagonistas & inibidoresRESUMO
For deconvolution applications in three-dimensional microscopy we derived and implemented a generic, accelerated maximum likelihood image restoration algorithm. A conjugate gradient iteration scheme was used considering either Gaussian or Poisson noise models. Poisson models are better suited to low intensity fluorescent image data; typically, they show smaller restoration errors and smoother results. For the regularization, we modified the standard Tikhonov method. However, the generic design of the algorithm allows for more regularization approaches. The Hessian matrix of the restoration functional was used to determine the step size. We compared restoration error and convergence behaviour between the classical line-search and the Hessian matrix method. Under typical working conditions, the restoration error did not increase over that of the line-search and the speed of convergence did not significantly decrease allowing for a twofold increase in processing speed. To determine the regularization parameter, we modified the generalized cross-validation method. Tests that were done on both simulated and experimental fluorescence wide-field data show reliable results.
Assuntos
Microscopia de Fluorescência/métodos , Algoritmos , Animais , Células CHO/citologia , Cricetinae , Imageamento Tridimensional , Funções Verossimilhança , Microtúbulos/ultraestruturaRESUMO
Thefluorescence microscope is routinely used to study cellular structure in many biomedical research laboratories and is increasingly used as a quantitative assay system for cellular dynamics. One of the major causes of image degradation in the fluorescence microscope is blurring. Deconvolution algorithms use a model of the microscope imaging process to either subtract or reassign out-of-focus blur. A variety of algorithms are now commercially available, each with its own characteristic advantages and disadvantages. In this article, we review the imaging process in the fluorescence microscope and then discuss how the various deconvolution methods work. Finally, we provide a summary of practical tips for using deconvolution and discuss imaging artifacts and how to minimize them.