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)

A 59-year-old woman with systemic lupus erythematosus was found to have marked hyperglycemia, extreme insulin resistance and abnormally high plasma immunoreactive insulin. Her circulating erythrocytes displayed a dramatic decrease of 125I-labeled insulin binding. Both the whole serum and purified IgG fraction strongly inhibited the binding of radiolabeled insulin to control erythrocytes. These results suggested, although indirectly, the existence of antibodies to insulin receptors in the serum of the patient. To directly investigate this issue, we used an enzyme-linked solid-phase immunoassay which allows the detection and enumeration of lymphocytes secreting antibodies towards insulin receptors. Peroxidase-conjugated anti-human immunoglobulin is used to reveal the binding of antibodies to insulin receptor-coated dishes. We demonstrated that the patient's mononuclear cells, when briefly incubated in Petri dishes with partially purified insulin receptor, were able to secrete immunoglobulins of G class specifically directed to the antigen. Moreover, only a fraction of the whole population of anti-insulin receptor antibodies was directed towards the insulin binding region of the receptor, seemingly corresponding to the auto-antibodies detected with conventional binding-inhibition assay.
 ...
PMID:Extreme insulin resistance due to anti-insulin receptor antibodies: a direct demonstration of autoantibody secretion by peripheral lymphocytes. 219 Jul 81

During a survey period of 28 years a total of 449 patients suffering respectively from pemphigus, systemic lupus erythematous and chronic nephritis was admitted to the hospital. Of the 286 patients who received glucocorticoid treatment 28 were found to have steroid diabetes (9.8%). The incidences of steroid diabetes in these diseases were as follows: pemphigus 20% (7/35), systemic lupus erythematous 12.5% (14/112), chronic nephritis 5% (7/139). Two thirds of the diabetic subjects appeared asymptomatic, while the remainder showed polydipsia and polyuria. Renal glucosuria was seen in 3 cases and hyperosmolar hyperglycemia in 4. Blood glucose level in 10 out of the 21 remaining cases was 8.9 +/- 1.5 mmol/L and in the other 11 cases 14.8 +/- 2.4 mmol/L. Generally, the treatment of steroid diabetes is not intricate. Satisfactory improvement was seen in about 80% of the patients if a strict line of therapy against primary diabetes was oriented. In this series 18 patients did well under the treatment either with reduction of steroid or with use of oral hypoglycemic agents or insulin or both. Their blood glucose levels returned to normal and urine sugar disappeared rapidly. Four of the 5 deaths were caused by their primary diseases. One died of pemphigus complicated with infection and shock exhibiting an ante mortem blood glucose level as high as 31.7 mmol/L, obviously hyperosmolar status being the predisposing factor. Due to the fact that most of the steroid diabetic patients were clinically asymptomatic, delayed or misbranded diagnosis was not infrequently seen.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Steroid diabetes: an analysis of 28 cases]. 280 46

In the studies reported here we demonstrate that bombesin decreases food intake in wolf (Canis lupus) pups without altering glucose or insulin levels. A high dose of cholecystokinin-octapeptide (CCK, 5 micrograms/kg) decreased food intake. CCK produced a transient increase in insulin, without altering glucose. Glucagon (0.5 mg/kg) failed to decrease food intake despite producing a marked hyperglycemia and hyperinsulinemia. Calcitonin was ineffective at decreasing food intake, although it did decrease the time spent feeding. These studies suggest a potential role for peripheral peptides in food regulation in the wolf.
 ...
PMID:The effect of peripheral administration of peptides on food intake, glucose and insulin in wolf pups. 355 Jul 28

Advanced glycosylation end products (AGEs) are thought to play an important role in the development of diabetic complications. Oxidative reactions are essential for the formation of some AGEs, termed glycoxidation products. Increased concentrations of pentosidine, one of such products, are found in tissue and serum in diabetes mellitus and in end-stage renal disease, suggesting that hyperglycemia and impaired renal function are important factors in AGE accumulation. We hypothesized that increased concentrations of pentosidine would also be found in pathological conditions associated with increased oxidative stress. We measured pentosidine in sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus, and diabetes. Increased serum pentosidine was found in RA (108.4 +/- 146.5 nmol/L, P < 0.002) and in diabetes (69.6 +/- 42.4 nmol/L, P < 0.001) as compared with healthy subjects (48.3 +/- 12.0 nmol/L). These results prove that AGEs may accumulate in the absence of hyperglycemia or impaired kidney function.
 ...
PMID:Increased concentrations of serum pentosidine in rheumatoid arthritis. 947 20

The chronic elevation of complement split products seen in many patients with systemic lupus erythematosus should be regarded as equivalent to silent hypertension, or hyperglycemia in a patient with incipient diabetes mellitus. Although the consequences may not be immediately evident, such patients should be monitored and perhaps even treated.
 ...
PMID:SLE: mechanisms of vascular injury. 956 36

Hyperglycaemia and/or oxidative stress can cause IgG to be modified by advanced glycation end products (AGE). Three patients with aggressive rheumatoid arthritis (RA) and vasculitis are described who have high titres of IgM antibodies against AGE-modified IgG (IgM anti-IgG-AGE). Diabetics and randomly selected patients with rheumatic diseases, including 50 additional RA patients, were tested for IgM and IgA anti-IgG-AGE by ELISA. AGE-modified proteins were detected using the nitroblue tetrazolium (NBT) colorimetric method. The presence of Nepsilon (carboxymethyl) lysine, an AGE modification, was detected on IgG-AGE by immunoblotting. A total of 20/41 (49%) rheumatoid factor (RF)-positive RA patients tested had IgM anti-IgG-AGE antibodies, 4/12 (33%) RF-positive systemic lupus erythematosus (SLE) patients, 3/5 RF-positive patients with primary Sjogren's syndrome (SS), and 3/5 RF-positive diabetics. All patients with RF-negative RA, SLE, SS, osteoarthritis (24), spondyloarthritis (15), adult-onset Still's disease (8), diabetes (25) and healthy controls (20) were anti-IgG-AGE negative. RF and IgM anti-IgG-AGE appeared to be a linked response. The IgM anti-IgG-AGE, along with IgG-AGE, may contribute to the pathogenesis of RA.
 ...
PMID:A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE. 997 55

The presence of insulin receptor antibodies is a rare cause of insulin resistance. Patients usually have a combination of hyperglycemia, insulin resistance, acanthosis nigricans, and autoimmune features. We report a patient with systemic lupus erythematosus and severe insulin resistance due to insulin receptor antibodies. The most striking aspect of the clinical presentation is the resistance to insulin therapy, with our patient unresponsive to doses of up to 154,075 units in a day. While on a low-dose glucocorticoid therapy, the patient had clinical improvement, and glucose levels subsequently became normal even without insulin and glucocorticoid.
 ...
PMID:Insulin receptor antibodies and insulin resistance. 1041 83

Heparan sulfate (HS) is the anionic polysaccharide side chain of HS proteoglycans (HSPGs) present in basement membranes, in extracellular matrix, and on cell surfaces. Recently, agrin was identified as a major HSPG present in the glomerular basement membrane (GBM). An increased permeability of the GBM for proteins after digestion of HS by heparitinase or after antibody binding to HS demonstrated the importance of HS for the permselective properties of the GBM. With recently developed antibodies directed against the GBM HSPG (agrin) core protein and the HS side chain, we demonstrated a decrease in HS staining in the GBM in different human proteinuric glomerulopathies, such as systemic lupus erythematosus (SLE), minimal change disease, membranous glomerulonephritis, and diabetic nephropathy, whereas the staining of the agrin core protein remained unaltered. This suggested changes in the HS side chains of HSPG in proteinuric glomerular diseases. To gain more insight into the mechanisms responsible for this observation, we studied GBM HS(PG) expression in experimental models of proteinuria. Similar HS changes were found in murine lupus nephritis, adriamycin nephropathy, and active Heymann nephritis. In these models, an inverse correlation was found between HS staining in the GBM and proteinuria. From these investigations, four new and different mechanisms have emerged. First, in lupus nephritis, HS was found to be masked by nucleosomes complexed to antinuclear autoantibodies. This masking was due to the binding of cationic moieties on the N-terminal parts of the core histones to anionic determinants in HS. Second, in adriamycin nephropathy, glomerular HS was depolymerized by reactive oxygen species (ROS), mainly hydroxyl radicals, which could be prevented by scavengers both in vitro (exposure of HS to ROS) and in vivo. Third, in vivo renal perfusion of purified elastase led to a decrease of HS in the GBM caused by proteolytic cleavage of the agrin core protein near the attachment sites of HS by the HS-bound enzyme. Fourth, in streptozotocin-induced diabetic nephropathy and during culture of glomerular cells under high glucose conditions, evidence was obtained that hyperglycemia led to a down-regulation of HS synthesis, accompanied by a reduction in the degree of HS sulfation.
 ...
PMID:Glomerular heparan sulfate alterations: mechanisms and relevance for proteinuria. 1065 15

Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
 ...
PMID:Newer uses of glucose-insulin-potassium regimen. 1120 54

Pregnancy markedly alters a normal woman's physiology and immune response mechanisms. The effect of pregnancy changes on the course of systemic lupus erythematosus (SLE) remains, however, speculative. Pregnant lupus patients are susceptible to pre-eclampsia, especially if they suffer lupus nephritis, and to steroid-induced hypertension and hyperglycemia. Fetuses are susceptible to placental insufficiency if antiphospholipid antibody or other procoagulant states are present, and to neonatal lupus if anti-Ro/La antibodies are present. Artificial reproductive technologies ("in vitro fertilization") can be safely used in SLE patients. Study of the physiology of pregnancy, for instance complement kinetics, may inform our understanding of SLE, and vice versa.
 ...
PMID:Lupus pregnancy. 1276 69


1 2 3 4 Next >>