Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and uremia; it is a common cause of acute renal failure in children. Although many microbial agents have been associated with HUS, only Escherichia coli O157: H7 has been clearly demonstrated to be a major cause of this illness. A case is presented of a healthy 4-year-old boy who had a recent varicella infection; when evaluated for HUS his blood and stool cultures both grew Salmonella montevideo and blood cultures grew group A beta-hemolytic streptococci. A stool cultured on MacConkey-sorbitol agar also grew E. coli O157: H7. An eightfold rise in serum antibodies to E. coli O157: H7 lipopolysaccharide was also demonstrated. The child recovered completely and was healthy 3 years later. Although this child had several infectious agents anecdotally associated with HUS, appropriate culture of stool showed that he also had E. coli O157: H7 infection. Previous cases thought to be due to other pathogens may similarly have been caused by co-infection with E. coli O157: H7.
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PMID:Hemolytic uremic syndrome due to Escherichia coli O157: H7 in a child with multiple infections. 161 38

The magnitude of response to lipopolysaccharide (LPS) by cells isolated from peritoneal dialysate (PDC) (n = 29) was compared to the response of monocytes (M) from hemodialysis (HD) patients (n = 8) and from normals (n = 9). Further studies compared monocyte (M) and PDC from 8 peritoneal dialysis (PD) patients, with adherence purification of PDC. The cells were cultured at 5 x 10(5)/ml with varying LPS concentrations for 1, 2, 8, 20 and 48 hrs. TNF was measured by L929 assay, PGE2 by RIA and Il-1 beta by ELISA. The data demonstrate a defect in the stimulated response of TNF and Il-1 beta by M from both HD and PD patients. A similar defect is also present in PDC. By contrast PGE2 response to stimulation with LPS does not differ in M from HD and normals. For TNF and PGE2 the depressed response of the PDC may be explained by the lower percentage of macrophages (M phi) if adherence purification has not been carried out. However Il-1 beta production by adherence purified M phi is significantly lower than monocytes, although greater than non-adherent cells. We describe alterations in uremic M and M phi function which may contribute to the clinically observed immune defect in uremia.
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PMID:Interleukin-1 beta, tumor necrosis factor, and prostaglandin E2 response after incubation of peritoneal cells and peripheral blood mononuclear cells with lipopolysaccharide. 168 Apr 12

Modification of the cellular immune response in uraemia is partly responsible for the increased susceptibility to infection found in dialysis patients. In order to study this further we have evaluated the in vitro production of tumour necrosis factor (TNF) by peripheral-blood monocytes (PBMCs) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure. The patients were subdivided into two groups according to the type of dialysis: those undergoing haemodialysis (HD; n = 12) and continuous ambulatory peritoneal dialysis (CAPD; n = 18). Results were compared with those of controls taken from healthy laboratory staff (n = 7). The experiments show that the secretion of TNF by of TNF by PBMCs in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 vs. 18.2 +/- 13.3 U/ml, mean +/- SD, p less than 0.001) and controls (81.3 +/- 38.7 vs. 18.1 +/- 6.6 U/ml, p less than 0.001). There was no significant difference between the CAPD group and controls. In vitro production of TNF fell slightly following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, p less than 0.05). We conclude from this study that TNF release from PBMCs is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD, in vitro. TNF release, however, is suppressed immediately following a single HD session. We suggest that HD rather than uraemia per se up-regulates monocyte secretion of TNF in vitro and that this is not an immediate response to activation by membrane polymer.
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PMID:Evaluation of the in vitro production of tumour necrosis factor by monocytes in dialysis patients. 180 56

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.
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PMID:Extrarenal production of calcitriol in normal and uremic humans. 198 15

By means of the lymphocyte transformation test (LTT), using the mitogens phytohemagglutinin (PHA), concanavalin A (ConA), lipopolysaccharide (LPS) E. coli and the antigens tuberculin (PPD) and O-streptolysin, a contribution should be made for the judgment of the functional capacity of the immune system--in particular of the cellular immunity--in uraemia patients with and without dialysis therapy. In 33 patients with different duration of the dialysis (0.5 to 130 months) and 15 retention patients who were not yet treated by means of dialysis the LTT was controlled with stimulant agents mentioned above. In these cases was shown that dialysis patients managed metabolically regularly did not show a significant restriction of the cellular immunity in the LTT (PHA-stimulation over 0.55 transformed cells, con-A-stimulation over 0.37 transformed cells). The not dialysed patients with chronic uraemia showed a distinct diminution of the unspecific T-cell transformation by PHA and ConA, whereas the antigen-induced stimulation (PPD, O-streptolysin) was not disturbed in this case as well. In the two cases the B-cell transformation (on LPS) was not significantly disturbed. There was a good concordance with the clinical findings: scarcely general infects, no shunt infections, relatively many organ losses by rejection after transplantation in the dialysis patients. The not yet dialysed retention patients revealed clinically a higher inclination to an infect. There were no own experiences about the course after transplantation without preceding dialysis. It is discussed in how far also immunological investigations may play a role in the establishment of the optimum management of the dialysis, the moment of the beginning with the dialysis and for the "more individual preparation of the transplantation".
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PMID:[Cellular immunity in dialysis patients using the lymphocyte transformation test (LTT) in comparison to conservatively treated patients with chronic terminal renal failure]. 352 44

A patient with uraemia undergoing chronic haemodialysis developed a unilateral effusion of the elbow joint. The chalky-white synovial fluid obtained from the joint contained many crystals that were identified as hydroxyapatite by infrared spectroscopy. The joint effusion showed chemotactic activity for healthy human neutrophils. Chemotactic activity of the lipopolysaccharide(LPS)-activated patient's serum was low compared to that of pooled healthy human sera, but the patient's serum did not have the inhibitor for the chemotactic factor. These findings suggest that the production of chemotactic factor in this patient's serum was decreased. The possible combined effects of the uraemic state and crystal-induced inflammation on the chemotaxis of neutrophil leukocytes are discussed.
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PMID:Hydroxyapatite associated arthritis in a patient undergoing chronic haemodialysis. 408 22

In addition to participating in protein synthesis in cells and tissues, L-arginine is essential for the synthesis of urea, creatine, creatinine, nitric oxide, and agmatine and influences hormonal release and the synthesis of pyrimidine bases. This places L-arginine, its precursors and its metabolites at the center of the interaction of different metabolic pathways and interorgan communication. Thus L-arginine participates in changing the internal environment in different but simultaneous ways, ranging from disposal of protein metabolic waste, muscle metabolism, vascular regulation, immune system function, and neurotransmission, to RNA synthesis and hormone-mediated regulation of the internal milieu. In normal rats, inhibition of the nitric oxide pathway results in systemic hypertension and decreased glomerular filtration rate and effective renal plasma flow. If the inhibition of this pathway is sustained, then glomerulosclerosis and death from uremia follow. Dietary intervention with L-arginine has resulted in amelioration of a number of experimental kidney diseases, such as those caused by subtotal nephrectomy, diabetic, nephropathy, cyclosporin A administration, salt-sensitive hypertension, ureteral obstruction, puromycin amino-nucleoside nephrosis, kidney hypertrophy due to high-protein feeding, and glomerular thrombosis due to administration of lipopolysaccharide. The present review addresses the current evidence for the beneficial effects of dietary intervention with L-arginine in a number of experimental renal diseases and describes the basis for the concept of L-arginine deficiency (absolute or relative) in certain settings in which supplementation of the diet with this amino acid may be beneficial.
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PMID:Role of arginine in health and in renal disease. 809 48

Macrophage dysfunction is considered an important contributory factor for increased propensity of infections in uremia. Because nitric oxide (NO) is believed to be an effector molecule of macrophage cytotoxicity, we propose that the dysfunction may be related to impaired NO synthesis. To verify this hypothesis, we evaluated macrophage NO synthesis in the presence of urea, a compound that accumulates in renal failure and is believed by some to be a uremic toxin. Macrophages (RAW 264.7 cells) were incubated with bacterial lipopolysaccharide to induce NO synthesis, whereas the test groups had various concentrations of urea in addition. NO synthesis was measured by assaying the supernatant for nitrites and nitrates by chemiluminescence. We observed that urea consistently produced a dose-dependent reversible inhibition of inducible NO production in macrophages, whereas parathormone, another toxin retained in uremia, had no such inhibitory effects. Further studies revealed that mRNA for inducible NO synthase was not inhibited by urea. We thus conclude that urea inhibits inducible NO synthesis in macrophages by a posttranscriptional mechanism and that this may be important in macrophage dysfunction of uremia.
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PMID:Urea inhibits inducible nitric oxide synthase in macrophage cell line. 943 93

Patients with chronic renal failure show an immunodeficiency characterized by frequent infectious complications and a low response to vaccinations. This is paralleled in vitro by a low T-cell proliferation on mitogenic stimuli because of an impaired costimulation by accessory cells. Furthermore, alterations of the cytokine profile are correlated with impaired immune function. The immune system is influenced by both uremia and renal replacement therapy. To evaluate the influence of hemodialysis on immune parameters, we studied patients before and after the initiation of chronic hemodialysis therapy. Fourteen patients with end-stage renal failure were tested before dialysis initiation and during the first 6 weeks of hemodialysis treatment. We determined the in vitro T-cell proliferation, as well as plasma levels of interleukin-6 (IL-6) and the release of IL-6 and IL-10 into culture supernatant poststimulation with lipopolysaccharide. After 6 weeks of intermittent hemodialysis, in vitro T-cell proliferation on stimulation improved significantly (stimulation index, 21.6 +/- 18.5 versus 58.1 +/- 45.5; P < 0.01). This improvement occurred regardless of whether synthetic dialyzers or cellulosic membranes were used for the initiation of dialysis. Plasma IL-6 levels, as well as IL-6 and IL-10 secretion, did not change during the study period. In patients with end-stage renal disease, the initiation of hemodialysis led to a significant improvement of in vitro T-cell proliferation. This effect may have a role for an improvement of immune function in vivo. The expected normalization of IL-6 and IL-10 production may be masked by cytokine induction through hemodialysis membranes.
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PMID:Initiation of hemodialysis treatment leads to improvement of T-cell activation in patients with end-stage renal disease. 1073 80

C57/B6 mice received intraperitoneal horse spleen apoferritin (4 mg) with lipopolysaccharide (0.05 mg); control mice received 0.15 M NaCl. Control and treated animals were killed weekly for 6 wk; blood and urine specimens were obtained, and tissue samples were secured. Treated animals showed evidence of significant chronic disease, with proteinuria, hematuria, and uremia. A mild glomerulonephritis was present at 2 wk, with significant proliferative glomerulonephritis at 4 wk, progressing to chronic disease with tubulointerstitial changes at 6 wk. Changes at each time period were uniform between animals. C3 mRNA was first detected by in situ hybridization at 3 wk. Message was restricted to proximal tubular and periglomerular epithelial cells. Presence of C3 message preceded the development of interstitial inflammation and fibrosis by 1-2 wk, and its location and intensity paralleled the evolving interstitial disease. Although extensive mesangial C3 protein deposits appeared early, there was never C3 message in glomeruli or infiltrating cells. Before C3 message became apparent, two cytokines known to up-regulate C3 transcription in vitro, IL-1 and IL-6, were detected by immunohistochemistry. The temporal sequence in this model is consistent with our hypothesis that local synthesis and activation of C3 in tubular epithelium is important to the interstitial component of chronic glomerulonephritis. The process is independent of the deposition of circulating complement in the glomerulus, but may be triggered by glomerular cytokines.
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PMID:Evidence of a role for local complement expression in a murine model of progressive glomerulonephritis. 1092 95


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