Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic causes for immune impairment in patients with severe chronic inflammatory diseases have not been clearly defined. Recently, the overproduction of poly(ADP-ribose) in resting lymphocytes with unrepaired DNA strand breaks has been suggested to contribute to immune dysfunction in adenosine deaminase-deficient patients. Our experiments have determined to what extent DNA damage and poly(ADP-ribose) synthesis might also explain the impaired mitogen responsiveness of PBL exposed to toxic oxygen species. Treatment of normal resting human lymphocytes with xanthine oxidase and hypoxanthine dose-dependently induced DNA strand breaks and triggered the rapid synthesis of poly(ADP-ribose). Subsequently, NAD+ and ATP pools decreased precipitously. Lymphocytes exposed previously to the enzymatic oxidizing system did not synthesize DNA after stimulation with PHA. However, if the medium was supplemented with 3-aminobenzamide or nicotinamide, two compounds that inhibit poly(ADP-ribose) formation, cellular NAD+ and ATP pools were preserved, and the lymphocytes responded vigorously to a mitogenic challenge. Excessive poly(ADP-ribose) synthesis, provoked by DNA strand breakage, may represent a common pathway that connects the immunodeficiency syndromes associated with (a) exposure of lymphocytes to toxic oxygen species during chronic inflammatory states, (b) adenosine deaminase deficiency, and (c) certain DNA repair disorders.
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PMID:Lymphocyte dysfunction after DNA damage by toxic oxygen species. A model of immunodeficiency. 395 May 45

An apparently healthy boy was suffering from recurrent Aspergillus infections. No classical conditions of immunodeficiency were found. Studies on the patient's phagocytic system revealed neutrophils and monocytes to function normally except in Aspergillus killing (microbicidal activity for bacteria and Candida was normal). Aspergillus killing mechanisms may be complex and peculiarly selective, possibly involving both oxygen-dependent and independent mechanisms.
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PMID:Defective phagocyte Aspergillus killing associated with recurrent pulmonary Aspergillus infections. 636 99

This report describes a case of osteomyelitis that did not respond to routine hyperbaric oxygen, surgical debridement, and intravenous antibiotics. The multiple sites of the osteomyelitis, the presence of skin lesions, and the unusual organism (Corynebacterium group JK, L form) that was isolated indicated that the patient might have an immunodeficiency, but none could be identified.
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PMID:Recurrent diffuse osteomyelitis involving the mandible. 658 31

We report two cases of human immunodeficiency virus (HIV) seropositivity and pulmonary hypertension seen at our institution and present a comprehensive literature review and available histopathologic findings of the association between HIV seropositivity and pulmonary hypertension. Studies and reviews pertaining to HIV seropositivity and pulmonary hypertension were identified through a MEDLINE search and reference citations. All studies and series found in the MEDLINE search were reviewed and are discussed in this article. Where data were available, comparisons and analyses were made between groups of reported cases of HIV seropositivity and pulmonary hypertension with regard to the following parameters: sex distribution, mode of acquiring HIV infection, presence or absence of the acquired immunodeficiency syndrome, CD4 cell counts, PO2 or oxygen saturation by pulse oximetry, concurrent lower respiratory tract infection, and histopathologic features. We conclude that there is strong evidence for pulmonary hypertension associated with HIV infection that is histologically indistinguishable from primary pulmonary hypertension. Consequently, HIV-seropositive patients with unexplained dyspnea should be evaluated for primary pulmonary hypertension. Prospective studies in HIV-positive patients are indicated.
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PMID:Primary pulmonary hypertension and the human immunodeficiency virus. Report of two cases and a review of the literature. 748 62

Hypocrellin A displays photoinduced antiviral activity, in particular against the human immunodeficiency virus (HIV), as does its counterpart, hypericin. Although hypocrellin A, like hypericin, executes an excited-state intramolecular proton transfer, it differs from hypericin in two important ways. Unlike hypericin, hypocrellin A absolutely requires oxygen for its antiviral activity. Also, whereas we have previously demonstrated that hypericin functions as a light-induced proton source, we do not observe that hypocrellin A acidifies its surrounding medium in the presence of light. These results are discussed in the context of the ground- and excited-state photophysics of hypericin and its mechanisms of photoinduced virucidal activity.
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PMID:Roles of oxygen and photoinduced acidification in the light-dependent antiviral activity of hypocrellin A. 749 16

An understanding of the contribution of reactive oxygen species to mutagenesis has been hampered by the vast number of different chemical modifications they cause in DNA. Even though many of these DNA alterations have been catalogued, the identification of specific lesions that cause mutations has depended on testing one modification at a time. In this study we present another approach to identify key mutagenic lesions from a pool of oxidatively modified nucleotides. dCTP was treated with an oxygen radical-generating system containing FeSO4, H2O2, and ascorbic acid. The modification products were separated by reverse-phase and anion-exchange HPLC and then incorporated by human immunodeficiency virus reverse transcriptase into a DNA that contains a target gene for scoring for mutations. One of the mutagenic species isolated was identified as 5-hydroxy-2'-deoxycytidine. It is incorporated efficiently into DNA and causes C-->T transitions in Escherichia coli at a frequency of 2.5%, which is more mutagenic than any previously identified oxidative DNA lesion.
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PMID:Reverse chemical mutagenesis: identification of the mutagenic lesions resulting from reactive oxygen species-mediated damage to DNA. 751 54

We have studied the effect of several environmental chemicals on the transient expression of a chloramphenicol acetyltransferase (cat) reporter gene linked to the promoter sequences in the long terminal repeat (LTR) of the human immunodeficiency virus type 1 (HIV-1). Aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) and benzo[a]pyrene cause a significant increases in CAT expression in mouse hepatoma Hepa-1 cells. The induction of CAT after TCDD treatment is abolished by administration of N-acetyl-L-cysteine or 2-mercaptoethanol and does not take place in a mutant cell line that lacks CYP1A1 enzymatic activity. Linker-scanning mutational analysis of transcription factor binding sites in the promoter revealed that both the NF kappa B and an adjacent aromatic hydrocarbon response element (AhRE) are required for TCDD-dependent CAT expression. In addition, mutation of the NFAT/AP-1 binding sites in the negative regulatory region of the promoter increases the magnitude of the TCDD effect. We conclude that induction of a functional CYP1A1 monooxygenase by TCDD stimulates a pathway that generates thiol-sensitive reactive oxygen intermediates which, in turn, are responsible for the TCDD-dependent activation of genes linked to the LTR. These data might provide an explanation for findings that TCDD increases infectious HIV-1 titers in experimental systems and for epidemiologic reports suggesting that exposure to aromatic hydrocarbons, such as found in cigarette smoke, is associated with an acceleration in AIDS progression.
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PMID:Dioxin activates HIV-1 gene expression by an oxidative stress pathway requiring a functional cytochrome P450 CYP1A1 enzyme. 760 37

Chronic granulomatous disease (CGD) represents an innate immunodeficiency: the reduced production of oxygen radicals in phagocytosing cells results in decreased ability to kill pathogenic microorganisms. The patients concerned suffer from severe recurrent infections due to bacteria and fungi. Prophylactic administration of trimethoprim-sulfamethoxazole, as usual in CGD-patients, has markedly reduced the incidence of bacterial infections. Now as before, however, there is a high risk to become affected by invasive fungal infections, mainly due to Aspergillus spp. which often are lethal. Therefore, a well-compatible antimycotic long-term prophylaxis effective against Aspergillus would be attractive. In the present study the compatibility of the oral triazole itraconazole was tested in 8 CGD-patients with high risk of Aspergillus infections. Itraconazole was administered in capsules with a dosage of 5.1 mg/kg body weight per day on an average for a mean range of 23 months. Periodically liver enzymes, renal retention and electrolytes were assessed as well as itraconazole serum levels. Aspergillus serology tests included complement fixation tests, IgG-ELISA, precipitation tests, IgE determination and Aspergillus-RAST. During the prophylactic treatment in all of the 8 patients no gastrointestinal side effects or hypersensitivity reactions were observed. Renal retention and serum electrolytes as well as liver enzyme values were in normal ranges with all patients. Itraconazole serum levels showed a marked intra- and interindividual variability. However, 82% of the peak levels were in ranges regarded as therapeutically effective for itraconazole. Under prophylaxis a clear decrease of Aspergillus IgG-ELISA values was observed in 5 of 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Long-term treatment of patients with itraconazole for the prevention of Aspergillus infections in patients with chronic granulomatous disease (CGD)]. 760 46

We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4+ lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4+ lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4+ lymphocyte function and the immunodeficiency in CVI.
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PMID:Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress. 763 46

Reactive oxygen species like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and, hence, in the activation and replication of human immunodeficiency virus type 1 (HIV-1) in human cells. Several antioxidant compounds and iron chelators have been shown to interfere with both NF-kappa B and HIV-1 activation under oxidative stress. Because 2,3-dihydroxybenzoic acid (DHB) and its ethyl ester derivative (DHB-EE) are potent oral iron chelators, we started to investigate their effects on monocytes treated with increasing H2O2 concentrations. These two compounds exert important protective effects against the cytotoxic effect of H2O2 as 300 microM DHB or DHB-EE increased cell survival from 30 to 85%. The treatment of monocytes with increasing amounts of H2O2 (from 0 to 3 mM) leads to the nuclear induction of NF-kappa B which is dose dependently inhibited by both DHB and DHB-EE. Addition of ferric ions to DHB only partially restores the NF-kappa B induction by H2O2, while this effect is almost completely restored by ferric ion addition to DHB-EE. Using spin trapping coupled to electron spin resonance, we have demonstrated that DHB and, to a lesser extent, DHB-EE trapped hydroxyl radicals produced by H2O2 photolysis. These data demonstrate that small aromatic molecules harboring both iron-chelating and antioxidant properties like DHB and DHB-EE can effectively interfere with the deleterious effects of H2O2 in monocytes where iron overload can be observed in HIV-1-infected patients.
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PMID:NF-kappa B transcription factor activation by hydrogen peroxide can be decreased by 2,3-dihydroxybenzoic acid and its ethyl ester derivative. 763 30


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