Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloperoxidase and eosinophil peroxidase were isolated from the bone marrow cells of rats treated with or without propylthiouracil (PTU) which caused bone marrow depression. PTU treatment decreased the activity of myeloperoxidase but not of eosinophil peroxidase using guaiacol as the electron donor. However, when KI,N-N'-dimethyl-p-phenylenediamine and pyrogallol were used as the electron donor, the activity of only eosinophil peroxidase was inhibited by PTU treatment. EPR spectra indicated that the structure of myeloperoxidase surrounding the heme iron changed from a rhombic form into an axial one by the repeated administration of PTU. Therefore, the inactivation of peroxidases by PTU treatment was accompanied by an alteration of their structures surrounding the heme.
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PMID:Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. 283 28

Studies were undertaken to evaluate factors capable of influencing the intensity of contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH) responses in mice. It is well known that the exposure of animals to ultraviolet radiation (UVR) causes a depression of CH and DTH responses whereas the injection of mice with nanogram quantities of pertussis toxin (PT) before sensitization results in greatly augmented CH responses following hapten challenge. Histopathology and biochemical quantitation of myeloperoxidase (MPO) activity in biopsies obtained from the challenged ears from normal, UVR-exposed, or PT-treated animals determined that a direct correlation existed between the intensity of the ear-swelling response and the degree of neutrophil infiltrate into the challenge site. Few neutrophils were observed to infiltrate into the ears of UVR-exposed animals when compared to normal animals, whereas a pronounced neutrophil infiltration was observed in the challenged ears of PT-pretreated animals. These observations led us to question whether tissue-infiltrating neutrophils, or their products, might be involved in controlling the intensity of CH and DTH responses. The direct injection of murine neutrophils, neutrophil homogenates, and a neutrophil granular fraction into the ear pinnae of normal mice resulted in a dosage-dependent ear-swelling reaction after 24 hours that was histologically similar to antigen-induced CH or DTH responses (primarily mononuclear cell infiltrate). Additional studies determined that an injection of elastase, collagenase, or peptides of elastin or collagen generated by elastase or collagenase treatment of insoluble elastin or collagen also caused a pronounced ear-swelling accompanied by a mononuclear cell infiltration. On the basis of these studies, coupled to experiments that demonstrated an inhibitory influence of alpha-1-antitrypsin (alpha 1-AT) on CH and DTH responses, we propose that neutrophil proteases may play an important role in regulating the intensity of CH and DTH responses in mice through their capacity to degrade extracellular matrix proteins whose peptide fragments are chemotactic for mononuclear cells and fibroblasts.
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PMID:The role of neutrophils in tissue localized cell-mediated immunologic responses: I. The intensity of contact-type and delayed-type hypersensitivity responses may be influenced by the extent of extracellular matrix degradation by neutrophil proteases. 285 42

Benzene is a myelotoxin which affects hemopoietic progenitor cells leading to bone-marrow depression as well as a genotoxin which causes chromosomal abnormalities including micronucleus formation. We have demonstrated previously that benzene administered to DBA/2 or C57B1/6 mice causes bone-marrow depression and increased prostaglandin E2 levels in bone marrow; both of these effects can be prevented by the coadministration of indomethacin, a selective inhibitor of prostaglandin synthase. We report, herein, that benzene (400-600 mg/kg body weight), under conditions where it depresses bone-marrow cellularity, also induces an increase in the frequency of micronucleus formation in polychromatic erythrocytes of C57B1/6 mice which is also prevented by the coadministration of indomethacin at levels that do not inhibit cytochrome P450 or myeloperoxidase. In Swiss Webster wild-type mice doses of benzene from 400 to 1000 mg/kg were without effect on marrow cellularity, but did induce the formation of micronucleated polychromatic erythrocytes which could be prevented by indomethacin. In contrast, DBA/2 mice, a strain highly sensitive to benzene, exhibited significant bone-marrow depression at a dose of benzene of 100 mg/kg body weight. Even at this low dose, benzene is too toxic toward developing erythrocytes to allow the evaluation of micronucleus formation. The frequency of induction of micronucleated polychromatic erythrocytes by benzene thus depends on the strain of mouse used. Furthermore, micronucleus formation appears to be an early and very sensitive indicator of benzene toxicity. A possible role for prostaglandin H synthase in the geno- and myelo-toxicity of benzene is discussed.
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PMID:The prevention of benzene-induced genotoxicity in mice by indomethacin. 292 13

Human subjects submitted to treatment with morphine show a severe depression of phagocytosis, killing properties and superoxide production both of their polymorphonuclear leukocytes and monocytes. Polymorphonuclear leukocyte adherence, chemotaxis, random migration, myeloperoxidase content, lysozyme content and lymphocyte Rosette E formation were poorly influenced. Methadone-treated subjects show a similar effect at phagocytic level but far less evident. These results confirm those previously found in animals and reinforce the evidence of a depressive role of morphine on phagocytic physiology.
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PMID:Morphine and methadone impact on human phagocytic physiology. 300 Sep 61

To better understand the process of time-related functional deterioration which occurs in human polymorphonuclear leukocytes (PMNs), we examined the effects of in vitro storage on multiple functional parameters of human PMNs. Single-donor, phlebotomy-collected PMNs were stored at both room temperature and 37 degrees C for 24 and 48 h, then compared to fresh cells from the same donor. Similar numbers of cells were recovered from each storage condition. Cell viability decreased after 37 degrees C storage for 48 h. Cells stored at room temperature for 24 h showed significant depression of multiple functions (bactericidal activity, chemotaxis, aggregation, superoxide production, and oxygen consumption) compared to fresh cells. They contained less vitamin B12 binding protein activity than fresh cells, and by fluorescence-activated cell-sorter analysis, their forward light scatter and membrane depolarization responses were abnormal. For all parameters examined, cells stored at 37 degrees C were more abnormal than cells stored at room temperature. Stored cells from a patient with myeloperoxidase deficiency lost bactericidal and chemotactic activity after storage at 37 degrees C for 24 h, but cells from a patient with chronic granulomatous disease retained their original bactericidal and chemotactic activity after 37 degrees C storage for 24 h. Radiation, in doses used to prevent graft vs. host disease in leukocyte-transfusion recipients (2500-5000 rads) caused a significant decrease in the mean percentage of continuous flow centrifugation leukapheresis (CFCL) collected PMNs capable of reducing nitroblue tetrazolium. Human PMNs show deterioration of multiple in vitro functions when they are stored and are susceptible to damage by radiation when they are collected by CFCL.
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PMID:Effects of storage and radiation on human neutrophil function in vitro. 369 76

Polymorphonuclear leucocytes function--Gey mobility, chemotaxis, NBT and myeloperoxidases--was studied in 29 patients with active viral infection and after clinic recuperation: 19 mumps meningitis, five measles, three varicella, one adenovirosis and one hepatitis A; these patients were compared with 31 age matched controls. Gey mobility and chemotaxis was markedly depressed during the acute period (p [0.05 and p less than 0.001 respectively), returning to normal values with clearing of infection. Also, myeloperoxidase decreases during acute period (p less than 0.05), but they don't return to normal values with clinic recuperation (p less than 0.05). NBT was similar in both groups. Studying mumps meningitis alone authors observed that results were similar to before: chemotaxis deficit (p less than 0.05) and myeloperoxidases (p less than 0,01). According to these results depression of polymorphonuclear function justifies only partially the higher predisposition to bacterial superinfection that some viral infections have.
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PMID:[Reduction of the function of polymorphonucleocytes: chemotaxis and myeloperoxidases in viral infections in childhood]. 609 60

Yearling steers were treated with ACTH to determine the effect of increased plasma cortisol concentration on bovine lymphocyte and polymorphonuclear leukocyte (PMN) function. The administration of ACTH caused a significant (P less than 0.01) increase in serum cortisol concentration and depression of lymphocyte blastogenesis in response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen was also depressed, but not significantly. Random migration by PMN was significantly enhanced by ACTH treatment, but there was no effect on ingestion of Staphylococcus aureus, nitroblue tetrazolium reduction, or antibody-dependent cell-mediated cytotoxicity by PMN. The iodination reaction, which evaluates the activity of the myeloperoxidase-hydrogen peroxide-halide antibacterial system of the PMN, was significantly impaired after ACTH treatment. These data indicate that specific parameters of lymphocyte and neutrophil function were impaired directly or indirectly by elevated in vivo concentrations of plasma cortisol.
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PMID:Effects of ACTH administration on bovine polymorphonuclear leukocyte function and lymphocyte blastogenesis. 628 May 26

Dose-dependent increases in alkaline phosphatase and acid phosphatase activities, decreases in myeloperoxidase activity of neutrophils and depression of lymphocyte glycerophosphate dehydrogenase and succinate dehydrogenase activities were discovered in rat nephropathy induced by mercuric chloride at doses of 0.1-1.0 mg/kg. These changes manifest the intensity of the oxidation-reduction process, the reduction of Kreb's cycle and alpha-glycerophosphatic shunt, the damage by peroxidation and the increase in catabolic processes. The morphometric data of nephron structure reflected the functional cell stress and they were compared with leucocyte enzyme status changes.
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PMID:Some aspects of testing drugs for nephrotoxicity in rats. 677 35

Polymorphonuclear leukocyte function and lymphocyte blastogenesis in response to mitogens were evaluated in castrated male cattle after the repeated administration of estradiol or progesterone. Polymorphonuclear leukocyte function was evaluated with the following five parameters: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity. The administration of high dosages of estradiol cypionate produced no measurable effect on the total or differential leukocyte count, neutrophil function, lymphocyte blastogenesis, or blood cortisol levels. The administration of high dosages of progesterone caused a significant enhancement of random migration by neutrophils and a depression of the activity of the myeloperoxidase-H2O2-halide antibacterial system (iodination) of the neutrophil. Progesterone administration did not cause a measurable effect on the lymphocyte blastogenic response to mitogens or the ability of polymorphonuclear leukocytes to ingest S. aureus, reduce nitroblue tetrazolium, or mediate antibody-dependent cell-mediated cytotoxicity. Progesterone did not cause a change in blood cortisol concentrations; therefore, the observed effects on polymorphonuclear leukocyte function were not due to alterations in blood cortisol concentrations. Impairment of the iodination reaction indicates that high dosages of progesterone interfere with an important bactericidal mechanism of the neutrophil.
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PMID:Effect of estradiol and progesterone on lymphocyte and neutrophil functions in steers. 706 28

The present study examined the effect of various unopsonized strains of influenza A virus on release of myeloperoxidase (MPO) and acid phosphatase in polymorphonuclear leukocytes (PMNL). These results were correlated with the effect that these same viruses had on bactericidal activity in PMNL. Several strains of virus inhibited the fusion of azurophil granules with phagosomes containing Staphylococcus aureus. These same strains inhibited the extracellular release of MPO from PMNL (39-59%) and caused depressed killing (42-77%). In contrast, one of the influenza viruses (X-47a) did not inhibit PMNL MPO release or killing. The data indicate a close relationship between the ability of influenza virus to ablate normal intracellular lysosome-phagosome fusion with subsequent depression of bactericidal functions of PMNL.
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PMID:Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity. 708 79


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