Summary
The goal of this study was to investigate the glycosylation profile of native immunoglobulin (Ig)G present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish ...this, lectin binding assays, detecting the accessibility of glycans present on IgG‐containing immune complexes by biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL), fucosylated tri‐mannose N‐glycan core sites (LCA), terminal sialic acid residues (SNA) and O‐glycosidically linked galactose/N‐acetylgalactosamine (GalNac‐L) were used. Patients with recent‐onset RA at baseline and after 3‐year follow‐up were investigated. We found that native IgG was complexed significantly more often with IgM, C1q, C3c and C‐reactive protein (CRP) in RA patients, suggesting alterations of the native structure of IgG. The total accessibility of fucose residues on captured immune complexes to the respective lectin was significantly higher in patients with RA. Moreover, fucose accessibility on IgG‐containing immune complexes correlated positively with the levels of antibodies to cyclic citrullinated peptides (anti‐CCP). We also observed a significantly higher accessibility to sialic acid residues and galactose/GalNAc glyco‐epitopes in native complexed IgG of patients with RA at baseline. While sialic acid accessibility increased during treatment, the accessibility of galactose/GalNAc decreased. Hence, successful treatment of RA was associated with an increase in the SNA/GalNAc‐L ratio. Interestingly, the SNA/GalNAc‐L ratio in particular rises after glucocorticoid treatment. In summary, this study shows the exposure of glycans in native complexed IgG of patients with early RA, revealing particular glycosylation patterns and its changes following pharmaceutical treatment.
The exposure of glycans in native IgG of patients with early RA detected by lectin‐based ELISA reveals particular glycosylation patterns that changes after the initiation of treatment of RA.
Aims: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp.
Methods and results: Patients were selected in two phases. An initial group of seven ...patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10–150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases.
Conclusions: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.
Lumbosacral transitional vertebrae (LSTV) is a common anatomic variant of the spine, characterized by the formation of a pseudoarticulation between the transverse process of the lumbar vertebrae and ...sacrum or ilium. LSTVs have been implicated as a potential source of low back pain – dubbed Bertolotti syndrome. Traditionally, LSTVs have only been subdivided into types I–IV based on the Castellvi radiographic classification system.
Solely identifying the type of LSTV radiographically provides no clinical relevance to the treatment of Bertolotti syndrome. Here, we seek to analyze such patients and identify a clinical grading scale and diagnostic-therapeutic algorithm to optimize care for patients with this congenital anomaly.
Patients presenting with back pain between 2011 and 2018 attributable to a lumbosacral transitional vertebra were identified retrospectively. Data was collected from these patients’ charts regarding demographic information, clinical presentation, diagnostic imaging, treatment and outcomes. Based on evaluation of these cases and review of the literature, a diagnostic-therapeutic algorithm is proposed.
Based on our experiences evaluating and treating these patients and review of the existing literature, we propose a clinical classification system for Bertolotti syndrome: we proposed a 4-grade scale for patients with Bertolotti syndrome based upon location, severity, and characteristics of pain experienced due to LSTVs.
Based on our experience with the cases illustrated here, we recommend managing patients with LSTV based on our diagnostic-therapeutic algorithm. Moving forward, a larger prospective study with a larger patient cohort is needed to further validate the treatment paradigm.
Rheumatoid arthritis (RA) is a debilitating inflammatory condition characterised by joint damage that affects the cervical spine most commonly at the atlantoaxial joint resulting in neck pain and ...myelopathy. The pathogenesis of RA involves the formation of a hyperplastic synovial tissue, termed pannus, which invades the local bone and causes osseous erosion. Here, we describe a case of rapid onset quadriparesis due to spinal cord compression at C5–C6 secondary to vertebral subluxation and mass effect from a large inflammatory pannus in the subaxial spine. Surgical decompression and resection of the subaxial pannus were performed, and the patient regained strength in all extremities. Histopathologic evaluation of the resected tissue confirmed the diagnosis of pannus over other more common epidural masses. Pannus formation commonly occurs in the peri-odontoid region; however, its presentation as a large soft tissue mass in the subaxial spine is not described in the current literature. Therefore, pannus should be considered in the differential diagnosis of epidural masses in the spine of RA patients. We use this case to discuss the pathology and radiological findings relevant to rheumatoid pannus formation in the subaxial cervical spine, as well as emphasise the importance of treatment in the context to severe degenerative disease.
Objective:
This study shall settle the question whether a perioperative single shot prophylaxis in connection with a ureteroscopic stone removal has an influence on the rate of postoperative urinary ...tract infections (UTIs) and inflammable complications or not.
Methods:
113 patients were included in this prospective randomized study. In 57 patients 250
mg Levofloxacin p. o. was given approximately 60 prior ureteroscopy, 56 patients had no prophylaxis. The evaluation of all data which were processed electronically was carried out with the help of a standardised questionnaire.
Results:
Postoperatively symptomatic urinary tract infections or inflammable complications of the urogenital tract were found in neither of the two groups. In the group without prophylaxis, the rate of the postoperative significant bacteriurias was significantly higher than in the group with prophylaxis (7 patients 12.5% vs. 1 patient 1.8%) (
p=0.026). In six cases there was an
E. coli bacteriuria additionally a Kl. pneumoniae and a not specified Staphylococcus bacteriuria were detected in further cases.
Conclusion:
Single shot prophylaxis using 250
mg Levofloxacin p. o. can be considered as cheap, the patient not burdened and regarding the missed selection pressure to nosocomial pathogens the preferred manner of perioperative antibiotic prophylaxis in ureteroscopic stone removal. In addition perioperative single shot prophylaxis may be beneficial in case of an unexpected intraoperative complication like e.g. ureter perforations.
Treatment of cells with agents that stimulate the release of arachidonic acid causes increased serine phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). Here we report that cPLA2 ...is a substrate for mitogen-activated protein (MAP) kinase. Moreover, phosphorylation by MAP kinase increases the enzymatic activity of cPLA2. The site of cPLA2 phosphorylation by MAP kinase, Ser-505, is identical to the major site of cPLA2 phosphorylation observed in phorbol ester-treated cells. Replacement of Ser-505 with Ala resulted in a mutant cPLA2 that is not a substrate for MAP kinase and causes little or no enhanced agonist-stimulated arachidonate release from intact cells. Taken together, these data indicate that MAP kinase mediates, at least in part, the agonist-induced activation of cPLA2.
Cytosolic phospholipase A2 (cPLA2) binds to natural membrane vesicles in a Ca(2+)-dependent fashion, resulting in the selective release of arachidonic acid, thus implicating cPLA2 in the hormonally ...regulated production of eicosanoids. Here we report that the treatment of Chinese hamster ovary (CHO) cells overexpressing cPLA2 with ATP or thrombin resulted in an increased release of arachidonic acid as compared with parental CHO cells, demonstrating the hormonal coupling of cPLA2. In contrast, CHO cells overexpressing a secreted form of mammalian PLA2 (sPLA2-II) failed to show any increased hormonal responsiveness. Interestingly, we have noted that the activation of cPLA2 with a wide variety of agents stimulates the phosphorylation of cPLA2 on serine residues. Pretreatment of cells with staurosporin blocked the ATP-mediated phosphorylation of cPLA2 and strongly inhibited the activation of the enzyme. Increased cPLA2 activity was also observed in lysates prepared from ATP-treated cells and was sensitive to phosphatase treatment. These results suggest that in addition to Ca2+, the phosphorylation of cPLA2 plays an important role in the agonist-induced activation of cPLA2.
The paper is based on the data of the 2009 DEPFET beam test at CERN SPS. The beam test used beams of pions and electrons with energies between 40 and 120
GeV, and the sensors tested were prototypes ...with thickness of
450
μ
m
and pixel pitch between 20 and
32
μ
m
. Intrinsic resolutions of the detectors are calculated by disentangling the contributions of measurement errors and multiple scattering in tracking residuals. Properties of the intrinsic resolution estimates and factors that influence them are discussed. For the DEPFET detectors in the beam test, the calculation yields intrinsic resolutions of
≈
1
μ
m
, with a typical accuracy of
0.1
μ
m
. Bias scan, angle scan, and energy scan are used as example studies to show that the intrinsic resolutions are a useful tool in studies of detector properties. With sufficiently precise telescopes, detailed resolution maps can be constructed and used to study and optimize detector performance.
The major dithiothreitol-resistant phospholipase A2 activity present in the cytosol of U937 cells has been purified greater than 200,000-fold by sequential chromatography on phenyl-5PW, ...heparin-Sepharose CL-6B, high-performance hydroxylapatite, TSK-gel G3000-SW, and Mono Q columns. This 110-kDa cytosolic phospholipase A2 is distinct from the relatively small (14-kDa) dithiothreitol-sensitive phospholipases A2 that are secreted from many cell types. This additional phospholipase A2 selectively hydrolyzes fatty acid at the sn-2 position of the glycerol and favors phospholipids containing arachidonic acid, which is the rate-limiting precursor for prostaglandin and leukotriene production. Interestingly, a greater than 5-fold increase in phospholipase A2 activity is noted as the calcium concentration increases from the levels found in resting cells to those observed in activated macrophages. We suggest that this enzyme and not the previously described secretory phospholipase A2 is activated by cytosolic effectors such as GTP-binding regulatory proteins and protein kinases to initiate the production of prostaglandins, leukotrienes, and platelet-activating factor. To distinguish this cytosolic enzyme from the previously described secretory ones, we suggest referring to it as cPLA2 for cytosolic phospholipase A2 and collectively referring to the secretory phospholipases A2 as sPLA2s.
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