Interaction of immune complexes with glomerular heparan sulfate–proteoglycans

Interaction of immune complexes with glomerular heparan sulfate–proteoglycans. The binding characteristics of cationic and more neutral immune complexes with heparan sulfate–proteoglycan enriched anionic sites of glomerular basement membrane and mesangial matrix were studied. Rat kidneys were treated either with buffers alone or buffers containing heparitinase or chondroitinase-ABC followed by perfusion with cationic or native immune complexes. Tissues were processed for immunofluorescence and transmission electron microscopy after fixation with glutaraldehyde or tannic acid glutaraldehyde. Kidneys perfused with radioiodinated immune complexes were processed for light and electron microscopic autoradiography. In addition, glomeruli from kidneys perfused with radioiodinated immune complexes were isolated and counted for radioactivity. By immunofluorescence the cationic immune complexes deposited linearly along the glomerular basement membrane. By electron microscopy, the cationic complexes localized mainly in the inner and outer layers of the glomerular basement membrane and to a certain extent in the mesangial matrix in a distribution that corresponded to previously documented anionic sites. Whereas heparitinase treatment abrogated the binding of cationic immune complexes in both glomerular basement membrane and mesangial matrix, chondroitinase-ABC treatment did not cause any decrease in binding. In contrast, more neutral immune complexes appeared to be nonspecifically trapped in the mesangium, and their distribution was unaffected by both enzymatic treatments. Light and electron microscopic autoradiography and counts of isolated glomeruli confirmed these findings. The results overall indicate that cationic immune complexes bind electrostatically to the heparan sulfate–proteoglycan enriched anionic sites of the glomerular basement membrane and mesangial matrix, while more neutral immune complexes are nonspecifically trapped in the mesangium of the renal glomerulus

Study of high field superconducting solenoids for muon beam cooling

The final beam cooling stages of a possible Muon Collider may require DC solenoid magnets with magnetic fields of 40-50 T in an aperture of 40-50 mm. In this paper we study possible solutions towards creating DC fields of that order using available superconductors. Several magnetic and mechanical designs, optimized for the maximum performance are presented and compared in terms of cost and size

Quench tests of Nb3Al small racetrack magnets

Two Cu stabilized Nb3Al strands, F1 (Nb matrixed) and F3 (Ta matrixed), have been made at NIMS and their Rutherford cables were made at Fermilab in collaboration with NIMS. A Small Race-track magnet using F1 Rutherford cable, the first Nb3Al dipole magnet in the world, was constructed and tested to full current at Fermilab. This magnet was tested extensively to full short sample data and its quench characteristics were studied and reported. The 3-D magnetic field calculation was done with ANSYS to find the peak field. The quench characteristics of the magnet are explained with the characteristics of the Nb3Al strand and Rutherford cable. The other Small Race-track magnet using Ta matrixed F3 strand was constructed and will be tested in the near future. The advantages and disadvantages of these Nb3Al cables are discussed

Optimal Management of High-Risk T1G3 Bladder Cancer: A Decision Analysis

Using a Markov model, Shabbir Alibhai and colleagues develop a decision analysis comparing cystectomy with conservative treatment for high-risk superficial bladder cancer depending on patient age, comorbid conditions, and preferences

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma

Abstract The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression. However, these reports have not penetrated the community, and many patients do not receive appropriate therapy. Additionally, several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease. The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of expanded use for both advanced and, potentially, localized disease. To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer, the Society for Immunotherapy of Cancer (SITC) convened a Task Force of experts, including physicians, patient advocates, and nurses, to address issues related to patient selection, toxicity management, clinical endpoints, as well as the combination and sequencing of therapies. Following the standard approach established by the Society for other cancers, a systematic literature review and analysis of data, combined with consensus voting was used to generate guidelines. Here, we provide a consensus statement for the use of immunotherapy in patients with bladder cancer, with plans to update these recommendations as the field progresses