RESUMEN
A new high radial resolution 2D multichannel Charge eXchange Imaging (CXI) diagnostic is under development for deployment at DIII-D. The diagnostic system will measure low-to-intermediate radial wavenumber carbon density fluctuations by observing the n = 8 - 7 (λ = 529.06 nm) C-VI emission line, resulting from charge exchange collisions between heating neutral beam atoms and the intrinsic carbon ion density. The new CXI diagnostic will provide measurements with ΔR â¼ 0.4 cm to access higher kr instabilities (kr < 8 cm-1) predicted to arise in the steep-gradient region of the H-mode pedestal. The CXI system will feature 60 fiber bundles in a 12 × 5 arrangement, with each bundle consisting of four 1 mm fibers. A custom optical system has been designed to filter and image incoming signals onto an 8 × 8 avalanche photodiode array. Additionally, a novel electronics suite has been designed and commissioned to amplify and digitize the relatively low-intensity carbon signal at a 2 MHz bandwidth. Forward modeling results of the active C-VI emission suggest sufficient signal to noise ratios to resolve turbulent fluctuations. Prototype measurements demonstrate the ability to perform high frequency pedestal measurements.
RESUMEN
A conceptual design for a 2D beam emission spectroscopy diagnostic system to measure ion gyro-scale plasma turbulence at Wendeslstein 7-X is described. The conceptual design identifies field-aligned viewing geometries and ports for cross-field turbulence measurements in the neutral beam volume. A 2D sightline grid covers the outer plasma region, and the grid configuration provides sufficient k-space coverage in radial and poloidal directions for ion temperature gradient and trapped-electron mode turbulence measurements. Emission intensity estimates, optical transmission losses, and detector noise levels indicate that the measurements will be sensitive to plasma density fluctuations as small as δn/n ≈ 0.5% with a bandwidth of 1 MHz. Implementation challenges include a small beam emission Doppler shift due to nearly radial heating beams and reduced optical throughput due to collection aperture limitations.
RESUMEN
Protein malnutrition is particularly deleterious in young individuals. An immunodeficient state is a well‑known functional consequence but alterations in thymic morphology remain unknown. Our aim is to analyze morphological characteristics of the rat thymus in a perinatal undernutrition and renutrition model we hypothesize these morphological alterations are reversible with early refeeding. Ninety-day-old Wistar rats were allowed to mate and divided into three groups: nourished (N normal 20% protein diet), undernourished (UN pre- and postnatal 5% protein diet until post-natal day 60 PND 60) and renourished (RN as UN but normal diet from PND 21 to 60). The thymi of 10 pups/group were submitted to macroscopic, histology, morphometry and scanning electron microscopy analyses. Body weight was highest in N and lowest in UN animals as expected but the thymic/body weight ratio remained similar in N and UN; this ratio was significantly higher in the RN group. UN thymi had a prevalence of type I collagen fibers, atrophic lobules and absence of a clear corticomedullary boundary. Thymic cortical component was decreased in UN. Apoptotic thymocytes were more frequently visualized in the UN thymi. N and RN thymi exhibited very similar morphology. Perinatal protein malnutrition induces drastic morphological alterations in rat thymi but these could be largely reversed with early renutrition. Functional studies are needed to assess if organ function mimics morphology in its recovery.
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Animales , Masculino , Femenino , Ratas , Timo/citología , Fenómenos Fisiológicos Nutricionales de los Animales , Microscopía Electrónica de Rastreo , Estudios de Evaluación como Asunto , Estudios de Evaluación como Asunto , Ratas WistarRESUMEN
Bacterial infection of the bone is a severe disease with complications, potentially including long-term physical disability. The diagnosis and therapy of osteomyelitis include several elements: histopathology, microbiology, radiologic imagining, as well as antibiotic and surgical therapy. Histopathologists differentiate between acute osteomyelitis (infiltration of cancellous bone with neutrophil granulocytes); specific osteomyelitis (epithelioid-like granulomatous inflammation, tuberculosis, mycotic infections); primary/secondary chronic osteomyelitis (lymphocytic infiltration); and special forms of chronic osteomyelitis (varying histomorphology, Brodie abscess, SAPHO syndrome). Another important task in the histopathological diagnosis of inflammatory bone diseases is to differentiate osteomyelitis from malignant entities (sarcoma, lymphoma). Therefore, biopsy samples should be of sufficient size for safe diagnosis. Clinical information and imaging as well as interdisciplinary teamwork between radiologists, microbiologists, orthopedic surgeons and pathologists is mandatory to verify these diagnoses.
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Infecciones Bacterianas/patología , Enfermedades Óseas Infecciosas/patología , Absceso/etiología , Absceso/patología , Adolescente , Adulto , Anciano , Infecciones Bacterianas/etiología , Biopsia , Enfermedades Óseas Infecciosas/etiología , Huesos/patología , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Osteítis/etiología , Osteítis/patología , Osteomielitis/etiología , Osteomielitis/patología , Factores de RiesgoRESUMEN
Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.
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Artritis Reumatoide/genética , Perfilación de la Expresión Génica , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteoglicanos/genética , Proteoglicanos/metabolismoRESUMEN
OBJECTIVE: To study the localization and cell type-specific expression of collagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA). METHODS: The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridization. Immunohistochemical detection of cell type-specific antigens was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. RESULTS: Collagenase 3 mRNA was detected in synovial membrane specimens of 21 of 36 RA patients (58%) and correlated with an increase in erythrocyte sedimentation rate (P<0.05) and C-reactive protein levels (P<0.005). Collagenase 3 mRNA was localized in fibroblast-like cells of the lining and sublining layers, and at the synovial membrane-cartilage interface. Four of 10 primary synovial fibroblast cell cultures showed basal expression of collagenase 3 mRNA, which was stimulated 2-4-fold upon interleukin-1beta or tumor necrosis factor alpha treatment and, in contrast to interstitial collagenase mRNA, 5-10-fold by increasing the intracellular level of cAMP. The stimulation by cAMP analogs was completely abolished by protein kinase A inhibitors. CONCLUSION: Some RA patients show collagenase 3 mRNA expression in the synovial membrane, which correlates with elevated levels of systemic markers of inflammation in these patients. In synovial fibroblasts, the expression of collagenase 3 and interstitial collagenase mRNA is differentially regulated by distinct protein kinase signal transduction pathways.
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Artritis Reumatoide/enzimología , Artritis Reumatoide/patología , Colagenasas/genética , Fibroblastos/metabolismo , Membrana Sinovial/citología , Membrana Sinovial/metabolismo , 1-Metil-3-Isobutilxantina/farmacología , Adenilil Ciclasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Bucladesina/farmacología , Células Cultivadas , Colforsina/farmacología , AMP Cíclico/metabolismo , Activación Enzimática/efectos de los fármacos , Femenino , Fibroblastos/química , Regulación de la Expresión Génica , Humanos , Hibridación in Situ , Masculino , Metaloproteinasa 13 de la Matriz , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa/farmacología , ARN Mensajero/biosíntesis , RadiografíaRESUMEN
OBJECTIVE: To analyze synovial membrane of patients with rheumatoid arthritis (RA) for the expression of unknown matrix metalloproteinases (MMP). METHODS: Degenerate oligonucleotides corresponding to highly conserved regions of the MMP gene family and the rapid amplification of cDNA ends (RACE) method have been used to search for new members of this gene family. MMP gene expression has been characterized by Northern blot analysis. RESULTS: We cloned a MMP cDNA from the synovial membrane that is completely identical to the recently published collagenase 3 cDNA derived from a human breast cancer cDNA library (Freije, et al: J Biol Chem 1994;269:16766-73). Collagenase 3 is expressed in parallel with interstitial collagenase and stromelysin 1 in RA and osteoarthritis (OA). Collagenase 3 gene expression was not detected in several normal human tissues. CONCLUSION: The expression of collagenase 3 in the synovial membrane in RA and OA suggests its involvement in articular tissue degradation.
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Artritis Reumatoide/enzimología , Colagenasas/biosíntesis , Osteoartritis/enzimología , Membrana Sinovial/enzimología , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Clonación Molecular , Colagenasas/genética , ADN Complementario/análisis , Femenino , Expresión Génica , Humanos , Masculino , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 13 de la Matriz , Metaloproteinasa 3 de la Matriz , Metaloendopeptidasas/biosíntesis , Metaloendopeptidasas/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Sondas de Oligonucleótidos/química , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisisRESUMEN
In patients with rheumatoid arthritis the synovial membrane of the affected joint is infiltrated with lymphoid cells which may be arranged in structures resembling germinal centers. We have directly isolated such infiltrates to determine whether B-cell clones within them are selected and expanded in a process analogous to that which normally takes place in the germinal centers in secondary lymphoid organs. The data suggest that an antigen-driven process leads to the accumulation of B cells in the synovial membrane. The finding of identical sequences in consecutive sections suggests that under conditions of chronic stimulation, memory B cells may enter a stage of differentiation in which they proliferate without further accumulation of somatic mutations. Further we see intraclonal diversity which underlines the germinal center-like character of these infiltrates and demonstrates that a microenvironment is built up in this nonlymphoid tissue which supports antigen-dependent differentiation of B cells. This is the first demonstration, to our knowledge, of a germinal center-like reaction outside lymphoid tissue.