Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

BACKGROUND/OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is an underrecognized and reversible condition in systemic lupus erythematosus (SLE) that could mimic neuropsychiatric lupus. Identification of any distinct clinical patterns is important as one would need to escalate rather than decrease or discontinue immune suppression in neuropsychiatric lupus. METHODS: We retrospectively identified and described 5 patients with SLE who were hospitalized and diagnosed with PRES from 2008 to 2013 in a tertiary medical center and reviewed relevant literature. RESULTS: Posterior reversible encephalopathy syndrome in SLE occurred in young women with age distribution from 19 to 37 years. At the time of presentation, all had hypertension (systolic blood pressures ranging from 150 to 220), moderate to severe disease activity (Systemic Lupus Erythematosus Disease Activity Index scores ranging from 11 to 41), and prototypical magnetic resonance imaging findings of PRES and nephritis (4 of 5 patients had biopsy-proven lupus nephritis). Seizures, headache, and confusion were the most common clinical symptoms. One patient had intracerebral hematoma, and 2 patients had cerebral petechial hemorrhages. All patients improved without any neurological deficits, with a mean hospital stay of 11.2 days. CONCLUSIONS: Systemic lupus erythematosus should be considered in the differential diagnosis of patients who present with PRES. One should have a low threshold for magnetic resonance imaging especially when neurological symptoms occur in young women with or without an established diagnosis of SLE and especially among those with active SLE, lupus nephritis, renal failure, and/or poorly controlled hypertension. Given the good prognosis of PRES in SLE patients with early supportive treatment, prompt recognition is crucial to institute appropriate management.

Ganglioside GM3 depletion reverses impaired wound healing in diabetic mice by activating IGF-1 and insulin receptors.

Ganglioside GM3 mediates adipocyte insulin resistance, but the role of GM3 in diabetic wound healing, a major cause of morbidity, is unclear. The purpose of this study was to determine whether GM3 depletion promotes diabetic wound healing and directly activates keratinocyte (KC) insulin pathway signaling. GM3 synthase (GM3S) expression is increased in human diabetic foot skin, ob/ob and diet-induced obese diabetic mouse skin, and in mouse KCs exposed to increased glucose. GM3S knockout in diet-induced obese mice prevents the diabetic wound-healing defect. KC proliferation, migration, and activation of insulin receptor (IR) and insulin growth factor-1 receptor (IGF-1R) are suppressed by excess glucose in wild-type cells, but increased in GM3S (-/-) KCs with supplemental glucose. Co-immunoprecipitation of IR, IR substrate 1 (IRS-1), and IGF-1R, and increased IRS-1 and Akt phosphorylation accompany receptor activation. GM3 supplementation or inhibition of IGF-1R or PI3K reverses the increased migration of GM3S(-/-) KCs, whereas IR knockdown only partially suppresses migration.

Deacetylated GM3 promotes uPAR-associated membrane molecular complex to activate p38 MAPK in metastatic melanoma.

GM3, the simplest ganglioside, regulates cell proliferation, migration, and invasion by influencing cell signaling at the membrane level. Although the classic N-acetylated form of GM3 (NeuAcLacCer) is commonly expressed and has been well studied, deacetylated GM3 (NeuNH2LacCer, d-GM3) has been poorly investigated, despite its presence in metastatic tumors but not in noninvasive melanomas or benign nevi. We have recently found that d-GM3 stimulates cell migration and invasion by activating urokinase plasminogen activator receptor (uPAR) signaling to augment matrix metalloproteinase-2 (MMP-2) function. However, the mechanisms by which d-GM3/uPAR increase MMP-2 expression and activation are not clear. By modifying the expression of d-GM3 genetically and biochemically, we found that decreasing d-GM3 expression inhibits, whereas overexpressing d-GM3 stimulates, p38 mitogen-activated protein kinase (MAPK) activity to influence MMP-2 expression and activation. p38 MAPK (p38) activation requires the formation of a membrane complex that contains uPAR, caveolin-1, and integrin α5ß1 in membrane lipid rafts. In addition, knocking down or inhibiting focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), or Src kinase significantly reduces d-GM3-induced p38 phosphorylation and activation. Taken together, these results suggest that d-GM3 enhances the metastatic phenotype by activating p38 signaling through uPAR/integrin signaling with FAK, PI3K, and Src kinase as intermediates. Elucidation of the mechanisms by which d-GM3, a newly discovered, potential biomarker of metastatic melanomas, promotes cell metastasis will help us to understand the function of d-GM3 in metastatic melanomas and may lead to novel GM3-based cancer therapies.

Enzyme co-localization in pea leaf chloroplasts: glyceraldehyde-3-P dehydrogenase, triose-P isomerase, aldolase and sedoheptulose bisphosphatase.

Nearest neighbor analysis of immunocytolocalization experiments indicates that the enzymes glyceraldehyde-3-P dehydrogenase, triose-P isomerase and aldolase are located close to one another in the pea leaf chloroplast stroma, and that aldolase is located close to sedoheptulose bisphosphatase. Direct transfer of the triose phosphates between glyceraldehyde-3-P dehydrogenase and triose-P isomerase, and from glyceraldehyde-3-P dehydrogenase and triose-P isomerase to aldolase, is then a possibility, as is direct transfer of sedoheptulose bisphosphate from aldolase to sedoheptulose bisphosphatase. Spatial organization of these enzymes may be important for efficient CO(2) fixation in photosynthetic organisms. In contrast, there is no indication that fructose bisphosphatase is co-localized with aldolase, and direct transfer of fructose bisphosphate from aldolase to fructose bisphosphatase seems unlikely.