Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is a disease characterized by the prolonged production of high-affinity autoantibodies resulting in direct and immune complex-mediated tissue damage. Because autoantibody responses occur over several years, memory B cells are likely to be involved. Interleukin-14 (IL-14) is a cytokine implicated in the generation and maintenance of normal memory B cells. Many of the actions of IL-14, including inhibition of antibody synthesis and upregulation of IL-14 receptors (IL-14R), are dependent on the formation of prostaglandin E (PGE) and subsequently cAMP. We observed that IL-14 induces phospholipase A(2) (PLA(2))-dependent release of arachidonic acid from phosphatidylcholine and phosphatidylinositol. Production of PGE is blocked by the PLA(2) inhibitor bromophenacyl bromide. Exogenous PGE (misoprostol) induces similar inhibition of antibody synthesis and increases in IL-14R as IL-14. Lymphocytes from patients with inactive SLE were noted to spontaneously produce PGE. Lymphocytes from normal donors produced PGE only after Sac-activation and IL-14 stimulation. Peripheral B and T lymphocytes from SLE patients, but not normal donors, spontaneously produced IL-14. Increased numbers of peripheral B lymphocytes from patients with inactive SLE expressed IL-14R, when compared to normal donors. Thus, increased production of IL-14 and PGE in SLE may result in expansion of a memory B-cell population capable of long-term autoantibody production. Further study will be necessary to confirm these preliminary findings and to examine in greater depth the regulation of PGE and IL-14 in SLE patients and normal donors.
 ...
PMID:A Potential Role for PGE and IL-14 (HMW-BCGF) in B-Cell Hyperactivity of Patients with Systemic Lupus Erythematosus. 1185 11

Deficiency of serum immunoglobulin (Ig)M is associated with the development of a lupus-like disease in mice. Recent studies suggest that classical complement components facilitate the clearance of apoptotic cells and that failure to do so predisposes mice to lupus. Since IgM is a potent activator of the classical complement pathway, we examined IgM binding to dying cells. IgM, but not IgG, bound to apoptotic T cells through the Fab' portion of the antibody. Exposure of apoptotic cell membranes to phospholipase (PL) A2 increased, whereas PLD reduced, IgM binding and complement activation. Absorption studies combined with direct plate binding assays, revealed that IgM antibodies failed to bind to phosphatidyl lipids, but did recognize lysophosphatidylcholine and the phosphorylcholine head group. Both iPLA(2) and cPLA(2) are activated during apoptosis. Since inhibition of iPLA2, but not cPLA2, attenuated IgM binding to apoptotic cells, these results strongly suggest that the endogenous calcium independent PLA(2), iPLA(2), is involved in the hydrolysis of plasma membrane phospholipids and exposure of the epitope(s) recognized by IgM. We propose that recognition of dying cells by natural IgM antibodies is, in part, responsible for complement activation on dying cells leading to their safe clearance.
 ...
PMID:I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation. 1220 80

Membranous nephropathy (MN) associated with malignancies is a well-known entity. However, its association with benign neoplasm is not broadly recognized. A 69-year-old man with recurrent nephrotic syndrome presented with pedal edema and proteinuria of 5 months' duration. Laboratory results showed hypoalbuminemia and hyperlipidemia. Proteinuria was estimated to be protein excretion of 3.5g/d. Studies were negative for viral hepatitis, syphilis, human immunodeficiency virus, autoimmune diseases, and paraproteinemia. Kidney biopsy disclosed MN with negative phospholipase A2 receptor (PLA2R) staining, favoring a secondary form of MN. Computed tomography detected a 7.6-cm duodenal schwannoma. Elective surgical resection was performed. Pathologic study showed that THSD7A (thrombospondin type 1 domain-containing 7A) was positive in both glomeruli and schwannoma. Commonly, secondary MN is related to underlying conditions, including lupus, hepatitis, and neoplasm, and can be medication induced. The risk for developing a concomitant neoplasm among patients with PLA2R-negative MN is up to 12 times higher than in the general population. Most of these neoplasms are malignancies, and the presence of autoantibodies directed at similar tissue targets is hypothesized as the potential mechanism. In our case, THSD7A may be the autoantibody that has linked the schwannoma and the development of MN. Although benign tumors rarely produce renal manifestations, effective treatment may lead to resolution of nephrotic syndrome.
 ...
PMID:Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report. 3045 84

Rodrigues, R, Franke, RA, Teixeira, BC, Macedo, RCO, Diefenthaeler, F, Baroni, BM, and Vaz, MA. Can the combination of acute alcohol intake and one night of sleep deprivation affect neuromuscular performance in healthy male adults? A cross-over randomized controlled trial. J Strength Cond Res 33(5): 1244-1251, 2019-The aim of this work was to perform a cross-over study to compare isolated and combined effects of alcohol intake and sleep deprivation on neuromuscular responses. Ten young and physically active male subjects were allocated to 4 conditions: (a) placebo intake + normal sleep (PLA + SLE); (b) alcohol intake + normal sleep (ALC + SLE); (c) placebo intake + sleep deprivation (PLA + SDP); and (d) alcohol intake + sleep deprivation (ALC + SDP). In each condition, volunteers ingested 1 g of alcohol per kg of body mass of alcoholic beer or nonalcoholic beer (placebo), followed by one night of normal sleep or sleep deprivation. In the next morning, neuromuscular performance (knee extensor isometric and concentric peak torque and time to task failure during the endurance test) and muscle activation were assessed. No differences were observed in the neuromuscular performance. We observed a significant reduction in quadriceps activation during the knee extensor isometric test in ALC + SDP compared with PLA + SLE (-20.8%; p = 0.02; d = 0.56). Our results demonstrated that acute alcohol intake and one night of sleep deprivation reduced quadriceps muscle activation without impact on neuromuscular performance.
 ...
PMID:Can the Combination of Acute Alcohol Intake and One Night of Sleep Deprivation Affect Neuromuscular Performance in Healthy Male Adults? A Cross-over Randomized Controlled Trial. 3090 73