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 high incidence of lung cancer in smokers is thought to be related to the direct exposure of bronchial and pulmonary cells to carcinogens in inhaled cigarette smoke. Using a 32P-postlabeling assay for chemically induced covalent DNA alterations, we found that unfractionated, relatively non-polar cigarette smoke components bound preferentially to lung and heart DNA in female ICR mice. After 6 days of topical treatment with cigarette smoke condensate (CSC) equivalent to a total of 4.5 cigarettes, covalent DNA damages was estimated to be 6.2, 5.7, 3.9 and 1.9 times higher, respectively, in lung, heart, skin and kidney than in liver, ranging from approximately 1 adduct in 5.4 +/- 0.7 X 10(6) DNA nucleotides in lung to 1 adduct in 3.3 +/- 0.6 X 10(7) DNA nucleotides in liver. Spleen DNA was virtually adduct-free. Adducts occupied two extensive zones, designated diagonal radioactive zone (DRZ) 1 and DRZ 2, on TLC fingerprints. Preference for lung and heart DNA was also observed in mice treated for 1 or 3 days. An inverse association appeared to exist between the tissue distribution of CSC-induced covalent DNA damage and the reported activity of enzymes catalyzing the metabolism of xenobiotics (cytochrome P-450 monooxygenases, phase II enzymes) and toxic oxygen species (superoxide dismutase, catalase). The results suggest that the well-known pulmonary and cardiovascular organotropism of cigarette-smoking-associated adverse health effects may, in part, have its origin in the inherent capacity of cigarette smoke components to induce lesions in lung and heart DNA in a tissue-specific manner. Possible mechanisms and health implications of the preferential binding of presumably aromatic CSC constituents to lung and heart DNA are discussed.
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PMID:Tissue distribution of covalent DNA damage in mice treated dermally with cigarette 'tar': preference for lung and heart DNA. 282 34

Rats injected with peptidoglycan-polysaccharide polymers derived from group A streptococcal cell walls (PG-APS) develop a chronic, remittant, erosive synovitis. Spleen cells from injected rats failed to proliferate when stimulated in vitro by Con A or PHA, unless nylon wool adherent cells were first removed. The suppression could also be reversed by removing phagocytic cells which had ingested carbonyl iron. Cells from control rats were suppressed in vitro by co-culture with unfractionated or nylon wool-adherent cells from PG-APS injected rats, and the suppressor activity was still expressed after exposure of the suppressor cells to 3,000 rad of irradiation. Addition of catalase and indomethacin to cultures only partially reversed the suppression. T lymphocytes from rats given a single arthropathic dose of PG-APS remained suppressed for at least 86 days after injection. Cells from rats given a low, non-arthropathic dose of PG-APS did not become suppressed. Cells from the Buffalo rat, which is resistant to development of PG-APS-induced chronic arthritis, showed less suppression than cells from the susceptible Lewis and Sprague-Dawley rat strains.
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PMID:Immunosuppressive macrophages induced by arthropathic peptidoglycan-polysaccharide polymers from bacterial cell walls. 306 53

Legionellae are widely spread in natural and man-made habitats. In many instances contaminated tap water has been linked to sporadic or endemic cases of human pulmonary infections, but it is not known why, in spite of frequent occurrence, legionellae only rarely cause disease. Monoclonal antibodies against Legionella pneumophila serogroup 1 (Philadelphia 1) were prepared in order to distinguish between subtypes of this serogroup. Balb/c mice were immunized i.v. three times with heat inactivated bacteria. Antibody formation was detected by an enzyme-linked immunosorbent assay (ELISA) technique using peroxidase-conjugated antimouse IgG. Spleen cells were then fused with NS-1 myeloma cells and cloned by limiting dilution. Four monoclonal antibodies were studied in detail. The study included 47 strains of L. pneumophila: 19 strains were of human origin and 28 were isolated from different environmental sources. Most were from tap water, but none from natural habitats. All strains belonged to serogroup 1 as defined by direct immunofluorescence (DFA) using monospecific FITC-labelled polyclonal antisera from rabbits. The strains were further characterized by beta-lactamase production, activity of catalase, oxidase and proteases, analysis of ubiquinones, and demonstration of membrane protein patterns by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A strong homogenicity between all the strains could be revealed by these methods independent of their origin. One of the monoclonal antibodies (B-1) was able to distinguish between human and environmental isolates. Eighteen of the 19 human strains reacted very strongly in DFA using antimouse immunoglobulin. No reaction, however, was seen with all of the environmental strains. Immunoblots were performed for characterization of the distinguishing feature using membrane complexes of all strains on nitrocellulose strips. The blots were incubated with antibody B-1, and immune complexes were detected by 125I-protein A. Broad intense blackening was seen between 22 and 70 kilodalton. This result suggests that no single protein, but rather a smaller component such as an oligosaccharide attached to constituents of different molecular weights, might be responsible for the discriminating reaction.
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PMID:Discrimination between clinical and environmental strains of Legionella pneumophila by a monoclonal antibody. 353 65

Amphotericin B (AmB) treatment before infection with the bacterium Listeria monocytogenes prolonged survival of AKR mice but shortened survival of C57BL/6 mice compared with survival of untreated infected controls. C57BL/6 mice were also more sensitive to the acute toxic effects of AmB than AKR mice, as were (C57BL/6 X AKR)F1 hybrid mice. Spleen cells and erythrocytes (RBCs) from the C57BL/6 and the F1 hybrid mice were both more sensitive to the lytic and lethal effects of AmB than corresponding cells from AKR mice. Biochemical analysis indicated that catalase levels in RBCs from C57BL/6 and F1 hybrid mice were about 60% of those found in RBCs from AKR mice. The lysis by AmB of RBCs from all these strains of mice was inhibited by catalase or incubation in a low-oxygen environment. These findings suggest that (i) the low catalase levels in C57BL/6 and F1 hybrid mice may limit the protection of cells from the oxidant damage involved in AmB action, and (ii) the toxicity which occurs at low concentrations of AmB in the mouse strains with low intracellular catalase levels may interfere with or ablate the AmB-induced increases in mouse resistance to L. monocytogenes infection.
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PMID:Toxicity and induction of resistance to Listeria monocytogenes infection by amphotericin B in inbred strains of mice. 377 Sep 45

The effects of dietary restriction of vitamin E and selenium were studied in male Long-Evans hooded rats. Weanling animals were maintained for 5-6 weeks on torula yeast-based diets, with or without the addition of vitamin E (150 IU/kg) or selenium (0.5 mg/kg), to form the following dietary groups: +E, +Se; +E, -Se; -E, +Se; -E, -Se, and a fifth group pair-fed with the -E, -Se group. This latter group exhibited a decreased rate of growth similar to the -E, -Se group. Lymphocyte blastogenesis in response to mitogens was decreased in animals fed the diets deficient in either vitamin E or selenium, and also in the pair-fed group. Very marked suppression of mitogen responses was seen in the doubly deficient group, as well as a greater loss of viability during culture. Spleen cell-mediated antibody-dependent lysis of chicken erythrocytes was increased in the doubly deficient group, although this difference could be abolished by the addition of catalase, but not indomethacin, to the culture medium. Dietary deficiency of vitamin E and selenium had no discernible effects on alveolar macrophage function, as measured by cell-mediated antibody-dependent cytolysis, killing of Staphylococcus aureus or regulation of T-lymphocyte blastogenesis.
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PMID:Effects of vitamin E and selenium deficiencies on rat immune function. 397 31

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.
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PMID:Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. 660 15

Solid tumors induce an angiogenic response by the host blood vessels to form a new vascular network for the supply of fresh nutrients and oxygen responsible for tumor growth. Furthermore, tumor growth and metastatic spread is abrogated or markedly reduced in the absence of neovascularization. Spleen T lymphocytes from tumor-bearing mice elicit a strong neovascular response. It is well known that certain T cell responses require the presence of active oxygen radicals. Because these metabolites are produced during tumor growth, we studied whether oxygen free radicals play a role in the angiogenesis induction by lymphocytes. In this study, we demonstrated that the administration of a free radical scavenger (EGb-761) to tumor-bearing mice, blocked the angiogenic response and decreased the lung metastatic incidence. On the other hand, when normal lymphocytes were incubated with the xanthine-xanthine oxidase system (X-XO), a known superoxide anion generator, this elicited a dose-response positive angiogenic reaction in normal recipient mice. No angiogenic response was observed in the absence of X-XO, or when EGb-761 or superoxide dismutase (SOD) plus catalase (CAT) were added to the incubation medium. These results suggest that free radicals are involved in some step of the angiogenic process, and that the EGb-761 treatments block this response due to the free radical scavenging activity of this compound.
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PMID:Inhibition of lymphocyte-induced angiogenesis by free radical scavengers. 752 98

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

The ameliorative effects of Opuntia vulgaris fruit extract (OE) were evaluated against methanol-induced haematological and biochemical toxicity in rats. The methanol-induced haematological and biochemical perturbation significantly decreased the levels of red blood cell (RBC), haemoglobin (Hb), haematocrit (Ht), serum total protein and increased glucose, cholesterol, and triglyceride levels in serum. Treatment of rats with methanol significantly increased lipid peroxidation (LPO) level and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes. OE treatment could increase significantly the levels of RBC, Hb, Ht and total protein, and decrease glucose, cholesterol and triglyceride levels in serum, and increase the activities of SOD, CAT and GPx in erythrocytes, when compared with methanol-treated group. Spleen histopathology showed that OE could significantly reduce the incidence of spleen lesion induced by methanol. These results suggested that OE could exhibit a potential source of natural antioxidants against methanol-induced haematological and biochemical disruption in rats. The protective effects of OE may be due to the modulation of antioxidant enzymes activities and inhibition of LPO.
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PMID:Haematological and biochemical toxicity induced by methanol in rats: ameliorative effects of Opuntia vulgaris fruit extract. 2142 78

Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS) accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2) and catalase (CAT). The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK), and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs) were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor) pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs) phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.
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PMID:Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway. 2831 30


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