Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of melphalan, an antineoplastic alkylating agent, on the activity of delta-aminolevulinic acid synthetase (ALA-S) was studied. When given in a single oral dose (20 mg/kg) to male rats. ALA-S activity in the spleen rapidly declined, reaching 9% of controls 7 days after administration. A return to control values occurred after 10 days, followed by a rebound increase in activity to 180% of controls at day 15. After melphalan administration, a gradual loss in spleen weight was observed until day 10, followed by a rebound increase in spleen weight at day 15. Spleen heme oxygenase activity was induced to 243% of controls 7 days after melphalan administration. However, by 20 days the activity was only 55% above controls. Bone marrow ALA-S activity declined to 38% of controls 3 days after treatment, followed by a return to controls after 7 days. The return to control values at day 15 was accompanied by a shift in the differential white blood cell count to the segmented form. Red blood cell counts and hemoglobin content were decreased to 77% of controls at day 7. Liver ALA-S was not appreciably affected by melphalan except for a decrease to 56% of controls at day 7. It is concluded that melphalan depresses the level of activity of the erythroid form of ALA-S in spleen and bone marrow but has less effect upon the level of activity of the nonerythroid form in the liver.
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PMID:Effect of melphalan on delta-aminolevulinic acid synthetase in the spleen, bone marrow and liver of rats. 689 78

Merocyanine 540 (MC540)-mediated photodynamic action is a novel approach for purging tumor cells from autologous remission bone marrow explants. The purpose of this study was to evaluate the effects of hemin (ferriprotoporphyrin IX), a potential source of pro-oxidant iron in bone marrow, on in vitro photodynamic inactivation of leukemia cells. Murine L1210 cells exhibited a progressive loss of clonogenicity when irradiated with broad-band visible light in the presence of MC540. Hemin had strikingly different effects on photokilling, depending on its contact time with cells, eliciting a sizable decrease in resistance after short-term (30-min) contact but a marked increase in resistance after long-term (24-h) contact. Similar trends were observed when cells were challenged with glucose/glucose oxidase, indicating that the responses apply to more than one type of oxidative stress. Immunoblot analyses revealed that the levels of inducible heme oxygenase (HO-1) and ferritin heavy (H) chain were substantially elevated 24 h after hemin addition. HO-1 increased relatively rapidly and maximized within 4 h after adding hemin, whereas H-ferritin increased more slowly in parallel with the development of hyperresistance, maximizing after 24-36 h. Desferrioxamine, an avid iron chelator, had no effect on HO-1 induction but inhibited both ferritin induction and the increase in cell resistance, suggesting that HO-mediated release of iron from hemin was necessary for triggering these responses. Spleen apoferritin was taken up by L1210 cells and strongly inhibited photokilling, further implicating ferritin involvement in hyperresistance. Photokilling was accompanied by free radical-mediated lipid peroxidation (thiobarbituric acid reactivity), which could be suppressed substantially by 24-h hemin preincubation. A plausible explanation for the long-term effects of hemin is that excess H-ferritin generated as a result of iron-regulatory protein deactivation sequesters toxic iron, which might otherwise catalyze damaging lipid peroxidation. Chronic oxidative release of hemin from bone marrow erythroid cells could compromise the efficacy of photopurging by making tumor cells more tolerant to photooxidative insult.
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PMID:Hyperresistance of leukemia cells to photodynamic inactivation after long-term exposure to hemin. 884 Sep 77

The pine vole, Microtus pinetorum, was evaluated as a laboratory animal model for infection with Rickettsia rickettsii. Voles demonstrated signs of acute disease, and 45% of infected animals died following intraperitoneal infection with 3 x 10(6) plaque forming units of R. rickettsii. Spleen, liver, kidney, lung, brain, testes and blood were analyzed for rickettsial burden by a quantitative PCR assay. The distribution of rickettsiae in tissues during the course of infection was determined by immunohistochemical staining and pathological changes in tissues were correlated with the clinical severity of infection. Quantitative RT-PCR assays were designed to measure the mRNA levels of the antioxidant enzyme genes for catalase, glutathione peroxidase, glutathione reductase, heme oxygenase, Cu-Zn superoxide dismutase (SOD) and Mn-SOD, and 2 housekeeping genes, actin and glyceraldehyde phosphate dehydrogenase. Tissues from acutely ill animals on days 2 to 6 of infection, convalescent animals, and uninfected control animals were studied. The number of transcripts of each enzyme gene was determined and compared to the degree of rickettsial infection present. These studies demonstrate that the pine vole is a valuable experimental model for studying infection with R. rickettsii. Our results provide the first experimental evidence that R. rickettsii causes alteration(s) of the anti-oxidant system in vivo.
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PMID:Rickettsia rickettsii infection in the pine vole, Microtus pinetorum: kinetics of infection and quantitation of antioxidant enzyme gene expression by RT-PCR. 1286 Jun 75

Kidney disease is a frequent consequence of heavy metal exposure and renal anemia occurs secondarily to the progression of kidney deterioration into chronic disease. In contrast, little is known about effects on kidney of chronic exposure to low levels of depleted uranium (DU). Study was performed with rats exposed to DU at 40 mg/l by chronic ingestion during 9 months. In the present work, a approximately 20% reduction in red blood cell (RBC) count was observed after DU exposure. Hence, three hypotheses were tested to determinate origin of RBC loss: (1) reduced erythropoiesis, (2) increased RBC degradation, and/or (3) kidney dysfunction. Erythropoiesis was not reduced after exposure to DU as revealed by erythroid progenitors, blood Flt3 ligand and erythropoietin (EPO) blood and kidney levels. Concerning messenger RNA (mRNA) and protein levels of spleen iron recycling markers from RBC degradation (DMT1 [divalent metal transporter 1], iron regulated protein 1, HO1, HO2 [heme oxygenase 1 and 2], cluster of differentiation 36), increase in HO2 and DMT1 mRNA level was induced after chronic exposure to DU. Kidneys of DU-contaminated rats had more frequently high grade tubulo-interstitial and glomerular lesions, accumulated iron more frequently and presented more apoptotic cells. In addition, chronic exposure to DU induced increased gene expression of ceruloplasmin (x12), of DMT1 (x2.5), and decreased mRNA levels of erythropoietin receptor (x0.2). Increased mRNA level of DMT1 was associated to decreased protein level (x0.25). To conclude, a chronic ingestion of DU leads mainly to kidney deterioration that is probably responsible for RBC count decrease in rats. Spleen erythropoiesis and molecules involved in erythrocyte degradation were also modified by chronic DU exposure.
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PMID:Renal anemia induced by chronic ingestion of depleted uranium in rats. 1837 46