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)

Nitric oxide (.NO) is synthesized by the enzyme nitric oxide synthase (NOS). There are 2 constitutive forms of NOS (cNOS) and 1 inducible form (iNOS). Cells containing cNOS rapidly and transiently produce small amounts of NO in response to agonists that raise cytosolic levels of free Ca2+, whereas cells expressing inducible iNOS produce large amounts of .NO for extended periods after a lag of several hours during which time the enzyme is induced. Until recently, the 2 constitutive isoforms of NOS were thought to be confined to endothelial cells (eNOS) and brain (bNOS or nNOS). However, eNOS and bNOS have been identified in an increasing variety of additional cells. Many, if not most, types of cells are capable of expressing iNOS in response to cytokines, endotoxin, and phagocytosis. Regulation of iNOS occurs at transcriptional, translational, and posttranslational levels. Because .NO is rapidly diffusible and soluble in hydrophobic and aqueous environments, it is well suited to its role as an intercellular messenger with the unique ability to penetrate solid tissue. However, it is rapidly inactivated by hemoglobin. The biochemistry of .NO is dominated by its rapid reaction with oxygen and transitional metals, notably iron. The former reaction may be protective, as when neutralizing superoxide (.O2-), or harmful in forming additional highly damaging radicals such as peroxynitrite. Interaction of .NO with iron-containing proteins has a number of sequelae, including the activation of guanylate cyclase, inhibition of mitochondrial respiration, and inhibition of cell division. Nitric oxide has been implicated in a number of conditions of orthopaedic interest, including inflammation, arthritis, osteoporosis, sepsis, ligament healing, and aseptic loosening of joint prostheses.
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PMID:Nitric oxide and its role in orthopaedic disease. 754 92

Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic chemotherapy, and is even rarer among recipients of bone marrow transplantation. Hemosiderosis, either idiopathic or caused by transfusion, appears to be another risk factor. We report a 3-year-old Chinese girl with transfusion-dependent Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received an allogeneic bone marrow transplantation. She was treated successfully with intravenous ampicillin. Our case adds to the clinical evidence that patients with iron overload are susceptible to listeriosis, particularly when they are immunocompromised and do not receive iron-chelation treatment.
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PMID:Listeria septicemia complicating bone marrow transplantation for Diamond-Blackfan syndrome. 764 Jan 84

Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis.
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PMID:Bovine myocardial epithelial inclusions. 768 Jan 78

13 premature babies (gestational age 31.1 +/- 0.9 weeks and birth weight 1586 +/- 261 g) were randomly assigned to receive recombinant human erythropoietin (200 U/kg i.v. three times a week during 4 weeks) or no (13 babies) as soon as haematocrit decrease < 30% between second and seventh week (TO). The two groups had similar gestational age, birth weight, Apgar score 1' and 5', O2-therapy, IPPV and volume of packed erythrocytes transfused before TO. Treatment was started at 30 +/- 0.5 days (range 21-42). At TO all subjects had not cardiopulmonary compromission, sepsis, O2-dependence, GMH-IVH > or = 2 degree grade and received iron and Vit. E by i.m. Result were evaluated through determination of hemoglobin, haematocrit, reticulocytes and volume of packed erythrocytes before and on days 7, 14, 21 and 28 of therapy. After rHuEPO the number of reticulocytes increased on days 21 and 28 of therapy (on day 21: 92.4 +/- 34.2 x 1000/L vs. 71.8 +/- 21.0, p < 0.10; on day 28: 116.2 +/- 42.9 vs. 83.8 +/- 23.2, p < 0.05); otherwise the number of transfusion (0.2 +/- 0.4 vs. 1.0 +/- 1.2, p < 0.10) and volume of packed erythrocytes (3.0 +/- 6.3 ml/kg vs. 14.9 +/- 15.9, p < 0.05) were reduced. Serum erythropoietin levels did not change during treatment, probably because, reducing the lowering of hemoglobin, hypoxic stimulus to increase of erythropoietin was suppressed.
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PMID:[Effects of recombinant human erythropoietin in the treatment of anemia of prematurity]. 773 26

Polyclonal antibodies were prepared to purified breast milk lactoferrin and used in an ELISA to measure plasma concentrations in investigations of various aspects of the inflammatory response. They were also used, in situ, to evaluate granulocyte lactoferrin content in disease states. The first series of studies addressed the putative role of lactoferrin in the pathogenesis of the hypoferremic, hyperferritinemic response to acute inflammation. Dissociation between the lactoferrin response and the iron related changes in rheumatoid arthritis and after alpha-interferon administration suggested that the relationship observed in acute and chronic bacterial infection may reflect coincidental effects of inflammatory cytokines. That lactoferrin does not mediate the inflammatory hypoferremic response was established by the finding that bone marrow transplant recipients, post-myeloablation, developed a hypoferremic response during septic episodes despite virtually undetectable plasma lactoferrin concentrations. The second series of investigations employed the plasma lactoferrin concentration as an index of granulocyte activation and function in a number of inflammatory conditions. Markedly increased initial plasma concentrations in acute pneumonia reflecting profound intravascular granulocyte activation were documented to predict sepsis related mortality. Plasma and granulocyte lactoferrin studies established that viral infection is associated with an acquired granulocyte lactoferrin deficiency. Plasma measurements indicated that asthmatics, even when clinically asymptomatic, have evidence of persistent granulocyte activation.
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PMID:Lactoferrin and the inflammatory response. 776 25

Reactive oxygen species (ROS) can be generated in experimental shock states through several different mechanisms. We measured ROS production in metabolically active liver mitochondria from rats rendered septic by cecal ligation and puncture. By polarography, the State 4 and State 3 respiration rates of liver mitochondria isolated from septic animals were no different from control organelles. During oxidation of succinate, however, nonenzymatic hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid by mitochondria from septic rats was increased, indicating generation of hydroxyl radical (OH.). Inhibition of electron transport at Complex I with rotenone had no effect on this pattern of OH. production, but rotenone and cyanide abolished the differences in OH. formation between control and septic liver mitochondria. Measurements of H2O2 release suggested that septic mitochondria will increase rates of H2O2 production in the presence of succinate. Additional investigations revealed no difference in the release of iron between septic and control mitochondria. When referenced to respiration rate, both OH. and H2O2 production were greater in septic liver mitochondria. The reproducible effect of sepsis on generation of reactive oxygen species by liver mitochondria utilizing FAD-linked but not NAD-linked substrates suggests that enhanced mitochondrial oxidative stress in sepsis is related to alterations in the activity of Complex II of the electron transport chain.
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PMID:Reactive oxygen species produced by liver mitochondria of rats in sepsis. 784 Jun 80

Due to the chemical nature of oxygen, its tendency to accept a single electron to create the superoxide radical, and the fact that every aerobic cell must deal with this difficult situation, the production of oxygen-derived free radicals is an almost universal accompaniment to cellular pathology. In sepsis or immunologic disease, the activated phagocyte becomes a major producer of active oxygen species, contributing to oxidative injury to host tissues. The resulting oxidative stress is seriously exacerbated by the availability of iron, liberated from the body's store of ferritin. The antioxidant vitamins and the body's antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) can help to restore and maintain proper oxidant/antioxidant balance.
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PMID:Oxygen-derived free radicals. 792 95

The examination of septic children has revealed characteristics of iron and red cell metabolism: deep and persistent hypotransferrinemia, normo- or hypersideremia, normal ferritin levels. Red cells of septic children contain low concentrations of ATPase, histidine, lipoproteins, there is compensatory enhancement of 2,3-DPG, G-6-PD SH-group activity. In terminal sepsis the activity of the above parameters drastically falls entailing hemolysis, anemia and severe hypoxia.
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PMID:[The metabolic activity of the erythrocytes and the characteristics of ferrokinetics in children with sepsis]. 802 Jul 13

In convalescents after and in patients with sepsis, purulent meningoencephalitis, severe pneumonia the study of iron metabolism provided biochemical criteria of iron excess: low serum transferrin against high transferrin iron, elevated ferritin. The risk of hyperferremia rises considerably after blood or erythrocyte transfusions. The liver got affected in the presence of infectious toxicosis. The authors believe it risky to practice uncontrolled administration of iron preparations in subjects recovering from severe bacterial and inflammatory diseases in view of threatening hemochromatosis.
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PMID:[The iron overload syndrome in patients with severe bacterial inflammatory diseases and convalescents]. 802 Jul 29

Shigellemia is rare in developed countries and might result from the emergence of unusually virulent strains. We compared systemic invasiveness markers of isolates from the blood of 3 temporally clustered patients with Shigella sonnei bacteremia in Boston with those of 11 unrelated contemporaneous strains from stools of people in New England. We found no difference between the two groups in O-chain length by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mouse 50% lethal dose, in vivo response to iron, and susceptibility to serum, which varied from moderately susceptible to ultrasusceptible. Mean intraperitoneal 50% lethal doses of smooth form I colonies for mice were equally low (10(5.8) CFU) in both groups, and the 50% lethal doses were lowered equally further in the two groups by predosing with iron to levels useful in mouse model sepsis studies. S. sonnei bacteremia may reflect compromised host defenses, not bacterial virulence.
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PMID:Comparative virulence of blood and stool isolates of Shigella sonnei. 819 2


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