Background. Growth factors, extracellular matrix and its receptor integrins are upregulated in various glomerular diseases. We investigated the mechanism of collaboration between integrins and platelet-derived growth factor (PDGF) in focal adhesion kinase (FAK)- and extracellular signal-related kinase (ERK)1/2-mediated signal pathways that lead to monocyte chemoattractant protein (MCP)-1 expression in cultured rat mesangial cells (MCs).
A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8, 1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.(Internal Medicine 40: 646-649, 2001)
High sucrose, high saturated fat western diets are increasingly leading to health issues such as obesity, metabolic syndrome and diabetes. Growing evidence also suggests that the western diet, and resulting metabolic abnormalities such as chronic hyperglycemia and inflammation, may increase the risk of cognitive decline and Alzheimer's disease (AD). The aim of this study was to assess changes in cerebral glucose metabolism and glial TSPO expression in response to obesity and intracerebroventricular Aβ infusion in vivo using PET. Three month old C57BL/J6 mice were fed either a standard (non-obese group) or high fat diet (obese group) for 3 months, and intracerebroventricularly infused with vehicle or Aβ-42. Fasting levels of blood glucose and insulin were measured as a marker of peripheral hyperglycemia, while brain [18 F]FDG uptake was assessed by PET a marker of cerebral metabolism. As a marker of deleterious gliosis, brain uptake of a TSPO ligand, [11 C]PBR-28, was assessed by PET. In vivo [11 C]PBR-28 uptake was confirmed by autoradiography of brain sections obtained from scanned mice. TSPO expression in glial subpopulations was confirmed by immunohistochemistry, co-staining with the glial markers CD-11b and GFAP. Obesity combined with A β infusion synergistically increased cerebral glucose metabolism and TSPO signals as assessed by PET. In autoradiographic sections, increased TSPO signals were associated with A β -infusion, but not obesity, although severe gliosis was observed by immunohistochemistry in both models of inflammation. In contrast, obesity-induced inflammation alone was associated with reduced TSPO signals detected by PET and autoradiography. FDG and TSPO may be useful imaging biomarkers for the identification of early-stage metabolic and inflammatory pathogenic changes in obesity associated with cognitive decline and AD risk. Increased brain [18 F]FDG uptake observed A β -infused mice may reflect increased metabolic demand resulting from gliosis or seizure activity. Surprisingly, obesity-induced inflammation was associated with decreased TSPO signals, which could potentially indicate qualitative differences in glial function between the two models of inflammation.
Objectives. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T cells and polyclonally activated B cells that produce autoantibodies. Five SLE patients who failed to respond to conventional immunosuppressants were treated with anti-CD20 antibody (rituximab) and their clinical manifestations and laboratory data were evaluated, including phenotypic analysis of B cells. Methods. Rituximab (375 mg/m2) was administered weekly for 2 weeks in five SLE patients who developed severe manifestations despite intensive treatment. Results. Rituximab resulted in rapid improvement (within several days) in clinical manifestations such as consciousness disorder, seizures, progressive sensory disorder, haemolytic crisis, cardiac function and laboratory data. The effects lasted 20 months in one patient; other patients were in remission for more than 6 months. Flow cytometric analysis revealed down-regulation of CD40 and CD80 expression on CD19-positive B cells 1 week after infusion of rituximab, and such down-regulation was seen for more than 7 months in two patients. Conclusions. Our pilot study provides sufficient evidence of excellent tolerability and high efficacy of rituximab therapy in refractory SLE. Rituximab not only reduced B-cell number and IgG levels but down-regulated CD40 and CD80 on B cells, suggesting possible disturbance of T-cell activation through these costimulatory molecules. Reduction of both quantity and quality of B cells suggests that rituximab could improve the disease course in patients with refractory SLE.
