Rheumatoid pannus presenting as a large epidural mass in the subaxial cervical spine: A case report.

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.

Onyiuke Grading Scale: A clinical classification system for the diagnosis and management of Bertolotti syndrome.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arthritis and its changes during therapy.

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.

Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases.

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.

Experimental study on a large animal model of a new thermoablation technique.

BACKGROUND: A novel technique of thermoablation, using a microtube to deliver pulses of hot water vapour, was tested on a large animal model in order to evaluate its efficacy and potential adverse effects. MATERIALS AND METHODS: The medical device consisted of a microtube extension connected to a hydropneumatic pump. Pulses of pure water were injected though the microtube where they were heated and delivered as vapour into the target zone. The method was tested on the liver of 12 healthy pigs, either during open surgery or percutaneously under ultrasounds. RESULTS: The technique was efficient and well-tolerated by the animals. Large volumes of necrotic tissue were created in a significantly short time compared to concurrent thermoablative techniques. CONCLUSION: Anticipating human application, this experimental study demonstrated a safe and efficient innovative thermoablation technique. The first human applications have been successfully performed and will be reported soon.

Molecular characterization of cytosolic phospholipase A2-beta.

We have isolated a cDNA encoding a 1012-amino acid polypeptide cPLA2-beta, that has significant homology with cPLA2-alpha in both the calcium-dependent lipid binding domain as well as in the catalytic domain. Transient expression of cPLA2-beta cDNA in COS cells results in an increase in calcium-dependent phospholipase A1 (PLA1) and PLA2 activities compared with vector-transfected cells. cPLA2-beta is markedly less selective for cleavage at sn-2 as compared with cPLA2-alpha and cPLA2-gamma. Northern analysis reveals a cPLA2-beta transcript of 8 kilobase pairs that is expressed in all the human tissues examined. With the identification of cPLA2-beta, the newly defined cPLA2 family now comprises three members that may have dramatically different mechanisms for regulation of expression and enzymatic activation.

[Tubo-ovarian actinomycosis, intrauterine device and chemotherapy for breast cancer]. / Actinomycose tubo-ovarienne, stérilet et chimothérapie pour cancer du sein.

Tubo-ovarian actinomycosis was observed after chemotherapy for breast cancer in a patient with an intrauterine device. Does chemotherapy increase the risk? How can it be prevented?

A novel calcium-independent phospholipase A2, cPLA2-gamma, that is prenylated and contains homology to cPLA2.

We report the cloning and characterization of a novel membrane-bound, calcium-independent PLA2, named cPLA2-gamma. The sequence encodes a 541-amino acid protein containing a domain with significant homology to the catalytic domain of the 85-kDa cPLA2 (cPLA2-alpha). cPLA2-gamma does not contain the regulatory calcium-dependent lipid binding (CaLB) domain found in cPLA2-alpha. However, cPLA2-gamma does contain two consensus motifs for lipid modification, a prenylation motif (-CCLA) at the C terminus and a myristoylation site at the N terminus. We present evidence that the isoprenoid precursor [3H]mevalonolactone is incorporated into the prenylation motif of cPLA2-gamma. Interestingly, cPLA2-gamma demonstrates a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid. cPLA2-gamma encodes a 3-kilobase message, which is highly expressed in heart and skeletal muscle, suggesting a specific role in these tissues. Identification of cPLA2-gamma reveals a newly defined family of phospholipases A2 with homology to cPLA2-alpha.

Endoscopic exploration and lymph node sampling of the axilla. Preliminary findings of a randomized pilot study comparing clinical and anatomo-pathologic results of endoscopic axillary lymph node sampling with traditional surgical treatment.

OBJECTIVE: To describe the technique of endoscopic exploration of the axilla. To compare this technique to open surgical treatment by comparing the following variables: operative time, peri-operative complications, duration of hospital stay, node's histology and morphologic aspects and esthetic results. MATERIALS: Standard instruments for traditional operative laparoscopy plus a lipo-aspirator (0.8 Bar). PATIENTS: Forty patients, 20 (group A) undergoing open surgery and 20 (group B) undergoing axilloscopy. All patients with early invasive breast cancer are eligible for conservative operative treatment. METHOD: Randomized study. The technique is described and preliminary results are presented. RESULTS: The operative time for axilloscopy is approximately double that for open surgery. A comparable number of lymph nodes is collected by axilloscopy and open surgery. The nodes collected by axilloscopy are more likely to be fractured. What is the clinical consequence? Two loco-regional relapses are observed in the endoscopic group. DISCUSSION: Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling. Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure. CONCLUSION: Operative time is increased for axilloscopy compared with open surgery. The techniques yield comparable anatomo-pathologic results. It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach.

Phospholipase C gamma-2 (Plcg2) and phospholipase C gamma-1 (Plcg1) map to distinct regions in the human and mouse genomes.

The phospholipase C gamma-2 (Plcg2) gene encodes an enzyme that plays a crucial role in intracellular signal transduction pathways. This enzyme is important because of its role in the generation of second messengers following the hydrolysis of phosphatidylinositol 4,5-bisphosphate. We have now determined the chromosomal location of this gene in the mouse and human genomes. An interspecific backcross involving AEJ/Gn and Mus spretus mice was used to localize the gene in mouse. A rodent/human somatic cell hybrid panel was used to map PLCG2 in the human genome. Our results position Plcg2 in the central region of mouse chromosome 8. We also show that PLCG2 maps to the long arm of human chromosome 16, in the region q22-qter. Plcg2 does not map near its most closely related family member, Plcg1, in either genome, indicating that the mammalian Plcg genes belong to a dispersed family.

Delineation of two functionally distinct domains of cytosolic phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding domain and a Ca(2+)-independent catalytic domain.

Cytosolic phospholipase A2 (cPLA2) associates with natural membranes in response to physiological increases in Ca2+, resulting in the selective hydrolysis of arachidonyl phospholipids. The isolation and sequence analysis of cPLA2 cDNA clones from four different species revealed several highly conserved regions. The NH2-terminal conserved region is homologous to several other Ca(2+)-dependent lipid-binding proteins. Here we report that the first 178 residues of cPLA2, containing the homologous Ca(2+)-dependent lipid-binding (CaLB) motif, and another recombinant protein containing the cPLA2(1-178) fragment placed at the COOH terminus of the maltose-binding protein (MBP-CaLB) associate with membranes in a Ca(2+)-dependent manner. cPLA2 and MBP-CaLB also bind to synthetic liposomes at physiological Ca2+ concentrations, demonstrating that accessory proteins are not required. In contrast, delta C2, a truncated cPLA2 lacking the CaLB domain, fails to associate with membranes and fails to hydrolyze liposomal substrates. However, both delta C2 and cPLA2 hydrolyze monomeric 1-palmitoyl-2-lysophosphatidylcholine at identical rates in a Ca(2+)-independent fashion. These results delineate two functionally distinct domains of cPLA2, the Ca(2+)-independent catalytic domain, and the regulatory CaLB domain that presents the catalytic domain to the membrane in response to elevated Ca2+.

cPLA2 is phosphorylated and activated by MAP kinase.

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.

Macrophage colony stimulating factor activates phosphatidylcholine hydrolysis by cytoplasmic phospholipase A2.

The macrophage colony stimulating factor (M-CSF) is required for the proliferation and differentiation of monocytes. Previous studies have demonstrated that M-CSF stimulation is associated with phosphatidylcholine (PC) hydrolysis and increased formation of both diacylglycerol (DAG) and phosphorylcholine. The present work extends those results by demonstrating that treatment of human monocytes with M-CSF is associated with increases in a cytoplasmic Ca(2+)-dependent activity which hydrolyzes 1-palmitoyl,2-arachidonoyl PC to arachidonic acid. The finding that this hydrolysis of PC is associated with increases in production of lysophosphatidylcholine indicates that M-CSF stimulates a cytoplasmic phospholipase A2 (cPLA2) activity. These results are supported by the demonstration that M-CSF induces cPLA2 gene expression. M-CSF-induced increases in cPLA2 mRNA levels were biphasic and corresponded with rapid (30-60 min) and delayed (24-72 h) increases in cPLA2 activity. The results demonstrate that this effect of M-CSF on cPLA2 expression is controlled at least in part by post-transcriptional stabilization of cPLA2 transcripts. The finding that M-CSF treatment is also associated with phosphorylation of the cPLA2 protein further suggests that expression of this enzyme is regulated at multiple levels. Finally, the stimulation of cPLA2 activity and arachidonate release is supported by increases in prostaglandin (PG) synthesis. In this regard, levels of both PGE2 and PGF2 alpha were increased in response to M-CSF. Taken together, these results indicate that M-CSF stimulates PC hydrolysis in human monocytes by inducing cPLA2 activity and thereby formation of eicosanoids.

Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-beta 2.

cDNAs corresponding to a previously uncharacterized phospholipase C were isolated from an HL-60 cell cDNA library. The cDNAs encodes a putative polypeptide of 1181 amino acids with a calculated molecular mass of 133,700 daltons. Comparison of the amino acid sequence of the predicted protein with those of five mammalian phospholipase C isoforms (PLC-beta 1, PLC-gamma 1, PLC-gamma 2, PLC-delta 1, and PLC-delta 2) revealed that the new enzyme is most closely related to PLC-beta 1 with an overall amino acid sequence identity of 48%. Thus, the new phospholipase C was named PLC-beta 2. The least similarity between PLC-beta 1 and PLC-beta 2 is apparent in the carboxyl-terminal 450 amino acids. Both PLC-beta 1 and PLC-beta 2 were purified from extracts of HeLa cells that had been transfected with vaccinia virus containing the corresponding cDNAs. Like other mammalian PLC isoforms, including PLC-beta 1, the catalytic activity of PLC-beta 2 was entirely dependent on Ca2+, and PLC-beta 2 preferred phosphatidyl-inositol 4,5-bisphosphate to phosphatidylinositol as substrate. Recently, the alpha subunit of the pertussis toxin-insensitive G-protein alpha q has been shown to activate PLC-beta 1 but not PLC-gamma 1 and PLC-delta 1. When alpha q purified from bovine brain was reconstituted with PLC-beta 1 or PLC-beta 2, no stimulation of PLC-beta 2 was observed in the presence of either AlF4- or guanosine 5-O-(3-thiotriphosphate) (GTP gamma S), whereas PLC-beta 1 activity was enhanced markedly in the presence of AlF4- and less markedly but significantly in the presence of GTP gamma S. These results suggest that the receptor-dependent stimulation of PLC-beta 1 and that of PLC-beta 2 may require different G-protein alpha subunits. (see also accompanying article (Lee, C. H., Park, D., Wu, D., Rhee, S. G., and Simon, M. I. (1992) J. Biol. Chem. 267, 16044-16047).

Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid.

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.