Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell damage of glomeruli and kidney arterioles seems to play a pivotal role in several pathologic situations, such as Gram-negative sepsis, glomerulonephritis, and acute renal failure. Bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) have been identified as potent inducers of apoptotic cell death in bovine glomerular endothelial cells. Both agents elicited apoptotic DNA laddering within 12 to 24 h. Basic fibroblast growth factor (bFGF) was generally described as a protective factor for endothelial cells against radiation-, TNF-alpha-, and UV-light-induced programmed cell death. Therefore, whether bFGF also affects apoptosis of microvascular endothelial cells was questioned. Surprising was that simultaneous treatment of glomerular endothelial cells with bFGF and either LPS or TNF-alpha left LPS-induced death unaffected, whereas TNF-alpha-induced death induction was potentiated, amounting to 48.9+/-6.3% versus 22.4+/-4.3% DNA degradation with TNF-alpha alone. Comparably, acidic FGF also selectively potentiated TNF-alpha-induced apoptosis. In mechanistic terms, bFGF synergistically increased TNF-alpha-induced mitochondrial permeability transition, the release of cytochrome c from mitochondria to the cytosol, and upregulation of the proapoptotic protein Bak and significantly enhanced activation of caspase-8 protease activity. In contrast, stress-activated protein kinase and nuclear factor kappaB activation, which represent primary signals of TNF/TNF receptor interaction, downregulation of the antiapoptotic protein Bcl-x(L), and caspase-3-like protease activation, were unaffected. As bFGF did not affect LPS-induced apoptotic cell death, bFGF also left LPS-induced Bak upregulation and Bcl-x(L) downregulation unaffected. The results point to a selective bFGF-mediated enhancement of distinct proapoptotic pathways induced by TNF-alpha in glomerular endothelial cells.
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PMID:Basic fibroblast growth factor selectively enhances TNF-alpha-induced apoptotic cell death in glomerular endothelial cells: effects on apoptotic signaling pathways. 1109 43

In the tropical north of Australia there are high rates of infections in Aboriginal children living in remote communities. In addition to the burden of respiratory infections, diarrhoeal disease and skin sepsis, there are high rates of acute rheumatic fever, outbreaks of poststreptococcal glomerulonephritis and gonococcal conjunctivitis, endemic trachoma and various intestinal parasites. A number of infections generally restricted to the tropics are also present and can cause disease in both indigenous and non-indigenous children. These include melioidosis, Murray Valley encephalitis and dengue on the east coast. With global warming, these infections may become more common and more widespread within Australia and the potential for establishment of introduced infections such as Japanese encephalitis and malaria may increase.
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PMID:Childhood infections in the tropical north of Australia. 1153 49

This review evaluates the various causes and management of acute renal failure (ARF) in children. ARF is defined as an abrupt decline in the renal regulation of water, electrolytes and acid-base balance, and continues to be an important factor contributing to the morbidity and mortality of critically ill infants and children. The common causes of ARF in children include acute tubular necrosis secondary to various causes (including congestive heart failure and sepsis), haemolytic uremic syndrome, and glomerulonephritis and urinary tract obstruction. Ischaemia, toxins (including drugs) as well as primary parenchymal disease, have to be considered and ARF can also be a complication of systemic disease. The basic principles of management are avoidance of life-threatening complications, maintenance of fluid and electrolyte balance, and nutritional support. Only a few patients require specific management of the underlying disorder, although it is important to diagnose these conditions. Knowledge about the use of drugs for the prevention of ARF is scarce. Mannitol, low-dose dopamine, calcium channel antagonists, atrial natriuretic peptide and albumin have been evaluated and, where possible, meta-analyses are cited. Mannitol treatment appears to be warranted prophylactically after paediatric renal transplantation. Albumin infusion can reverse prerenal ARF in children with nephritic syndrome. For treatment of the complications of hyperkalaemia and volume overload, salbutamol, insulin and glucose infusion and diuretics such as furosemide and sodium bicarbonate, are discussed. All of the major dialysis modalities (peritoneal dialysis, haemodialysis and continuous haemofiltration) can be used to provide equivalent solute clearance and ultrafiltration. The indication for, and the choice of the modality depend on the patient requirements and on local resources, and should involve the care of a paediatric nephrologist. Peritoneal dialysis requires minimal equipment and infrastructure, is easy to perform and remains the favoured modality of renal replacement therapy in children. However, continuous haemofiltration is an excellent alternative to peritoneal dialysis in patients with ARF and severe fluid overload. Dialysis remains the most important tool to bridge the time needed for recovery of renal function. There is increasing evidence that more intense use of dialysis may improve the overall prognosis.
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PMID:Acute renal failure in children: aetiology and management. 1173 64

Over the past year, human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor (MIF) in a number of diseases that had originally been studied in animals. In addition to sepsis, rheumatoid arthritis, glomerulonephritis and inflammatory lung disease, elevated MIF levels have been described in patients suffering from ulcerative colitis, inflammatory neurological diseases and cancer. Cellular studies indicate that in addition to macrophages, MIF affects the activities of CD4+ and CD8+ T cells, natural killer cells, fibroblasts and endothelial cells, actions that may explain the contribution of MIF to inflammatory diseases and cancer. Molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins (Jab1, PAG and p53) that control cellular growth and proliferation; however, how interactions with these proteins fit into a general scheme to explain MIF's biological activity has not been elucidated. The three-dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF-associated diseases, they may provide good targets for therapeutic intervention.
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PMID:Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. 1175 24

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS.
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PMID:Pulmonary renal syndrome: a 4-year, single-center experience. 1177

Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
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PMID:Macrophage migration inhibitory factor. 1178 58

Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS), but similar reports in children are lacking. We describe two children with MDS-associated steroid-responsive nephrotic syndrome (NS). Patient 1, who had MDS with myelofibrosis, presented with hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer. During initial prednisone treatment proteinuria markedly diminished and partial but transient hematological improvement occurred. Relapse subsequently occurred that manifested by overt NS and pancytopenia. High doses of prednisolone led to remission of the renal disease, but hematological remission did not occur. Persisting pancytopenia and repeated infections terminated in sepsis, 2 years after the onset of the MDS. Patient 2, who had refractory anemia with clonal monosomy 19, presented with bowel disease, hepatosplenomegaly, anemia and non-organ-specific autoantibodies. Prednisone led to both clinical and hematological remission. The hematologic disease relapsed 12 months later, when nephrotic-range proteinuria, hematuria and mild azotemia were also found. Corticosteroid treatment led to long-lasting renal and hematologic remission, maintained by a small dosage of prednisone. In both patients, renal biopsy findings were consistent with those seen in idiopathic NS. A Medline search disclosed 16 cases of glomerulopathy in the course of MDS in adult patients. Clinical features included NS, usually accompanied by renal insufficiency with acute, chronic, or rapidly progressive glomerulonephritis. On biopsy, membranous nephropathy, crescentic or mesangial proliferative glomerulonephritis, and AL amyloidosis were found. We conclude: (1) that glomerular disease may be present and should be searched for in patients with MDS and (2) that MDS can be added to the list of rare conditions associated with corticosteroid-responsive NS in children.
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PMID:Glomerular involvement in myelodysplastic syndromes. 1179 99

Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
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PMID:Macrophage migration inhibitory factor. 1189 4

Nitric oxide (NO) plays an important regulatory/modulatory role in a variety of inflammatory conditions. NO is a small, short-lived molecule that is released from a variety of cells in response to homeostatic and pathologic stimuli. It may act as a vasodilator and a platelet inhibitor and may interfere with adhesion molecules to prevent neutrophil adhesion. NO release may also lead to the formation of highly reactive species such as peroxynitrite and stable nitrosothiols and may cause mitochondrial damage and nitration of protein tyrosine residues. In addition, NO inhibits cell proliferation via inhibition of polyamine synthesis and cell uptake and may well act as a 'brake' on the proliferative response following cytokine exposure. All three isoforms of nitric oxide synthases are found in the kidney during inflammation. The site of NO release impacts significantly on its net function and structural impact. NO plays a protective role in many forms of immune injury, such as nephrotoxic serum-induced glomerulonephritis, autoimmune tubular interstitital nephritis, and experimental allergic encephalomyelitis. NO overproduction in sepsis, after cytokine exposure, inducible NO synthase transcription, and local inflammation can autoinhibit endothelial NO synthase, leading to selective renal and mesenteric vasoconstriction.
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PMID:Role of nitric oxide in inflammatory conditions. 1196 94

The present study reports epidemiological data on renal disorders in children in Venezuela. Information was obtained from 14 centers for the period January through December 1998. A total of 3,624 patients were evaluated as either a first outpatient consultation or as a first hospital admission. Nearly 70% of the patients could be grouped in one of the following categories: (1) urinary tract infections (32%), with detection of abnormalities of the urinary tract in 25%, (2) metabolic disorders (28%), mainly idiopathic hypercalciuria and hyperuricosuria, (3) glomerulonephritis (9.5%). The other 30% corresponded to urolithiasis 7%; renal tubular acidosis 5.6%; nephrotic syndrome 4.5%; primary hematuria 4.2%; acute renal failure 2.8% (43% were secondary to acute dehydration, 15% to birth asphyxia, 14% to septicemia, and 23% to multiple factors); chronic renal failure 1.6% (secondary to glomerulopathies, predominantly focal glomerulosclerosis, structural abnormalities of the urinary tract, hereditary disorders, and renal hypoplasia/dysplasia); miscellaneous diseases 4.8%. Hence, the spectrum of renal disorders in Venezuela is wide, sharing similarities with countries of both the developed and developing world. These data will hopefully contribute to the development of national healthcare policies appropriate to the epidemiology of the country.
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PMID:Renal diseases in children in Venezuela, South America. 1217 77


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