Polymeric IgA are sulfated proteins

AbstractThe main sulfated proteins secreted by rabbit mammary gland tissue had Mr of ∼67 000, 63 000 and 23 000, and one component which most likely corresponded to proteoglycans had a diffuse electrophoretic mobility (Mr>200 000). The sulfate groups in the 67–63 kDa proteins were mostly linked to carbohydrates. These proteins and the 23 kDa protein were co-purified and identified to heavy chains of immunoglobulin A (IgA) and J chain, respectively. Sulfation of α-chains also occurred in rat mammary and rabbit lacrimal glands. We conclude that polymeric IgA which are produced by plasma cells and released in secretion fluids after transcytosis through epithelia are sulfated

Stability of an oscillating tip in Non-Contact Atomic Force Microscopy: theoretical and numerical investigations

This paper is a theoretical and a numerical investigation of the stability of a tip-cantilever system used in Non-Contact Atomic Force Microscopy (NC-AFM) when it oscillates close to a surface. No additional dissipative force is considered. The theoretical approach is based on a variationnal method exploiting a coarse grained operation that gives the temporal dependence of the nonlinear coupled equations of motion in amplitude and phase of the oscillator. Stability criterions for the resonance peak are deduced and predict a stable behavior of the oscillator in the vicinity of the resonance. The numerical approach is based on results obtained with a virtual NC-AFM developped in our group. The effect of the size of the stable domain in phase is investigated. These results are in particularly good agreement with the theoretical predictions. Also they show the influence of the phase shifter in the feedback loop and the way it can affect the damping signal

Complex primary total hip arthroplasty

SummaryAlthough total hip arthroplasty is now a classic procedure that is well controlled by orthopedic surgeons, some cases remain complex. Difficulties may be due to co-morbidities: obesity, skin problems, muscular problems, a history of neurological disease or associated morphological bone deformities. Obese patients must be informed of their specific risks and a surgical approach must be used that obtains maximum exposure. Healing of incisions is not a particular problem, but adhesions must be assessed. Neurological diseases may require tenotomy and the use of implants that limit instability. Specific techniques or implants are necessary to respect hip biomechanics (offset, neck-shaft angle) in case of a large lever arm or coxa vara. In case of arthrodesis, before THA can be performed, the risk of infection must be specifically evaluated if the etiology is infection, and the strength of the gluteal muscles must be determined. Congenital hip dysplasia presents three problems: the position and coverage of the cup, placement of a specific or custom made femoral stem, with an osteotomy if necessary, and finally lowering the femoral head into the cup by freeing the soft tissues or a shortening osteotomy. Acetabular dysplasia should not be underestimated in the presence of significant bone defect (BD), and reconstruction with a bone graft can be proposed. Sequelae from acetabular fractures presents a problem of associated BD. Internal fixation hardware is rarely an obstacle but the surgical approach should take this into account. Treatment of acetabular protrusio should restore a normal center of rotation, and prevent recurrent progressive protrusion. The use of bone grafts and reinforcement rings are indispensible. Femoral deformities may be congenital or secondary to trauma or osteotomy. They must be evaluated to restore hip biomechanics that are as close to normal as possible. Fixation of implants should restore anteversion, length and the lever arm. Most problems that can make THA a difficult procedure may be anticipated with proper understanding of the case and thorough preoperative planning

DNA properties investigated by dynamic force microscopy

In this work, we show that by varying the experimental conditions, the driving amplitude, a dynamic force microscope allows DNA properties to be selectively imaged. The substrate on which the DNA is fixed is a silica surface grafted with silanes molecules ended with amine groups. Use of small oscillation amplitudes favors the attractive interaction between the tip and the sample, while use of large amplitudes renders the contribution of the attractive interaction negligible. Particularly, at small amplitudes, the images show that the attractive interaction is strongly enhanced along the DNA. This enhancement is found to be amenable with a model considering a narrow strip of randomly oriented dipoles on each side of the molecule. This work should provide new insights on the DNA interaction and conformational changes with localized charges

Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18kDa Translocator Protein Radioligand [18F]DPA-714

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuroinflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuroinflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuroinflammation for detection, monitoring, and research in MS

[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model.

International audienceINTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5-1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa Translocator Protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Today, diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. The present study aims to investigate the potential of [18F]DPA-714 to monitor in vivo inflammatory processes at a preclinical stage via positron emission tomography (PET). METHODS: RA was induced in Dark Agouti rats by subcutaneous injection of inactivated mycobacterium tuberculosis. Development of arthritis clinical signs was investigated daily and the severity of the disease evaluated. Animals were imaged at the peak of inflammation using [18F]DPA-714 and a small-animal PET-CT tomograph. RESULTS: The first clinical signs appeared at 10 days post-injection, with a peak of inflammation at 20 days. At this time, PET-analyses showed a clear uptake of [18F]DPA-714 in swollen ankles, with mean values of 0.52 +/- 0.18%ID/cc for treated (n = 11) and 0.19 +/- 0.09 for non-treated (n = 6) rats. A good correlation between [18F]DPA-714's uptake and swelling was also found. Immunohistochemistry showed an enhanced TSPO expression in hind paws, mainly co-localized with the macrophages specific antigen CD68 expressing cells. CONCLUSION: These preliminary results demonstrates that the TSPO 18 kDa specific radioligand [18F]DPA-714 is adapted for the study and follow up of inflammation linked to RA in our experimental model, suggesting also a strong potential for clinical imaging of peripheral inflammation

Stability of an oscillating tip in Non-Contact Atomic Force Microscopy: theoretical and numerical investigations.

This paper is a theoretical and a numerical investigation of the stability of a tip-cantilever system used in Non-Contact Atomic Force Microscopy (NC-AFM) when it oscillates close to a surface. No additional dissipative force is considered. The theoretical approach is based on a variationnal method exploiting a coarse grained operation that gives the temporal dependence of the nonlinear coupled equations of motion in amplitude and phase of the oscillator. Stability criterions for the resonance peak are deduced and predict a stable behavior of the oscillator in the vicinity of the resonance. The numerical approach is based on results obtained with a virtual NC-AFM developped in our group. The effect of the size of the stable domain in phase is investigated. These results are in particularly good agreement with the theoretical predictions. Also they show the influence of the phase shifter in the feedback loop and the way it can affect the damping signal