Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.
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PMID:Simultaneous detection of ferritin and HIV-1 in reactive microglia. 141 82

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.
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PMID:Siderotic cerebral macrophages in the acquired immunodeficiency syndrome. 158 Jul 55

As a result of the AIDS crisis, public and physician pressure have increased the utilization of autologous blood products. Attitudes about homologous blood transfusion, however, have changed dramatically in recent years. A large segment of the population undergoing elective surgery is elderly and therefore has a significant incidence of cardiovascular disease and a slow response of the erythropoietic system when acute anemia occurs. However, preoperative autologous blood donation programs require 2-5 weeks to complete; the average yield is only 2.2 units per patient. As a consequence, autologous predonation is underused and homologous transfusion cannot be completely avoided in all patients. For several years recombinant human erythropoietin (rHuEPO) has been available and has been successfully used in the treatment of patients with renal anemia. This study evaluated the effect of r-HuEPO on patients with preoperative autologous blood collection. METHODS. Ten patients of both sexes scheduled for hip arthroplasty underwent a preoperative autologous program. During a period of 23 days prior to surgery autologous blood donation was performed with 7.5 ml/kg withdrawal on four occasions, the last one 5 days prior to surgery. Five patients were randomly treated with subcutaneous injections of rHuEPO (Erypo, Cilag GmbH, Sulzbach; Distributor: Fresenius AG, Oberursel, FRG) 200 IU/kg seven times, starting 3 days after the first blood withdrawal. All patients (n = 10) received oral iron therapy with iron sulphate 304 mg/die (= 100 mg iron/die). Patients with hypertension or recent myocardial infarction were excluded from the study. The hemoglobin level before donation had to be at least 11.0 g/dl. On each study day, a complete blood count and platelets, differential, and reticulocyte count were determined by standard methods as were transferrin, ferritin, and total iron-binding capacity. Blood loss and blood consumption during and after the operation were registered. The indication for blood transfusion (autologous/homologous) was based on hemoglobin values, which were not acceptable below 8.5 g/dl. RESULTS. No side effects of rHuEPO treatment were observed. Blood loss ranged from 650 to 1100 ml intraoperatively and 400 to 950 ml postoperatively with no differences between the groups. Patients with rHuEPO had no autologous red cell concentrates (aRCC) during the operation; two of them had two units of aRCC on the 2nd postoperative day. Two of the patients in the control group had intraoperative blood transfusions (2 and 3 units aRCC, respectively); all patients in this group were transfused postoperatively: 12 of the 20 units collected were utilized. At the onset of the operation the mean hemoglobin value in patients with rHuEPO was 13.5 +/- 0.4 g/dl compared to 11.3 +/- 0.3 g/dl in the controls. Reticulocytes increased significantly during the investigation period. On the 2nd, 3rd, and 4th days of autologous blood collection and before the onset of surgery, the number of reticulocytes was significantly greater in rHuEPO patients than in the controls. Further laboratory variables such as transferrin, ferritin, and total iron-binding capacity did not change significantly during the investigation period; there were no significant differences between the two groups. DISCUSSION. The results of the present study show that rHuEPO leads to an increase in reticulocytes with maintenance of hemoglobin levels during the phlebotomy program. As a consequence, patients with anemia and particular contraindications to homologous blood derivatives (irregular antibodies, Jehovah's Witnesses) may be able to undergo major surgery successfully. The possibility of shortening the intervals between phlebotomies would seem to be of major advantage; our data also suggest that an aggressive autologous blood collection program would increase yields over present programs. In our institute a minimum hemoglobin level of 11.5 g/dl is accepted for autologous donation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Recombinant erythropoietin in autologous blood donation]. 192 12

To look for possible defects in cells of the monocyte/macrophage system, blood monocytes from patients infected with human immunodeficiency virus (HIV) were cultured on hydrophobic Teflon for 7 days and their ability to differentiate into mature macrophages in the presence of serum was followed. The following parameters were studied as indicative of successful terminal maturation: (1) the expression of maturation-associated antigens (transferrin receptor, surface transferrin, the BA-2 antigen, MAX antigens), (2) the disappearance of the MOP15 antigen, and (3) a more than 20-fold increase in intracellular ferritin concentration. It was found that the patients' blood monocytes did not differentiate in vitro but rather remained immature precursor cells. If the same holds true in vivo, the results could indicate that the pathophysiology of the acquired immunodeficiency syndrome (AIDS) may be, to a large extent, linked with the functional consequences of this impaired monocyte-to-macrophage maturation.
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PMID:Defective monocyte to macrophage maturation in human immunodeficiency virus infection. 234 11

Elevated serum ferritin levels have been observed in several disease states including various malignancies, inflammatory states, and the acquired immunodeficiency syndrome (AIDS). This discussion will examine the normal sequence of events in T cell activation and proliferation, as well as the various defects in these events, and monocyte/macrophage and NK cell activity seen in AIDS patients. Further, the potential role of a serum suppressor factor as a contributor to the profound immunosuppression seen in AIDS will be discussed, as will evidence suggesting that ferritin may be this factor. A model is presented to explain mechanisms by which ferritin might suppress immune function and further studies to elaborate these mechanisms are proposed.
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PMID:The potential role of serum ferritin in the pathogenesis of acquired immune deficiency syndrome (AIDS). 267 19

The laboratory evaluation of anemia begins with a complete blood count and reticulocyte count. The anemia is then categorized as microcytic, macrocytic or normocytic, with or without reticulocytosis. Examination of the peripheral smear and a small number of specific tests confirm the diagnosis. The serum iron level, total iron-binding capacity, serum ferritin level and hemoglobin electrophoresis generally separate the microcytic anemias. The erythrocyte size-distribution width may be particularly helpful in distinguishing iron deficiency from thalassemia minor. Significant changes have occurred in the laboratory evaluation of macrocytic anemia, and a new syndrome of nitrous oxide-induced megaloblastosis and neurologic dysfunction has been recognized. A suggested approach to the hemolytic anemias includes using the micro-Coombs' test and ektacytometry. Finally, a number of causes have been identified for normocytic anemia without reticulocytosis, including normocytic megaloblastic anemia and the acquired immunodeficiency syndrome.
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PMID:Laboratory evaluation of anemia. 357 35

Ferritin has been linked to a variety of immunosuppressive effects on cell-mediated immunity. Therefore, serum ferritin was measured by radioimmunoassay in patients with acquired immune deficiency syndrome (AIDS), AIDS-related complex (ARC) and healthy heterosexual men. 13 of 15 patients with AIDS and 4 of 15 with ARC had ferritin levels greater than 300 micrograms/dl. This study suggests that the levels of serum ferritin increase with the progression of immune deficiency and might play a role in the pathogenesis of cell-mediated immune deficiency in AIDS.
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PMID:Serum ferritin in acquired immune deficiency syndrome. 373 94

Ferritin is a complex polypeptide which functions primarily as an iron-storage protein. Ferritin may also play a role in the modulation of immune function. It is known to suppress several global measures of the immune response. Specifically, ferritin may mask and/or down-regulate expression of cell surface molecules important in T-cell activation and effector functions. These interactions may become pathologically significant in conditions where marked hyperferritinemia occurs, most notably malignancies and the acquired immunodeficiency syndrome (AIDS). Levamisole appears to possess immunomodulatory properties and be capable of disrupting the interaction of ferritin with T lymphocytes. This activity may be therapeutically useful in conditions of ferritin excess, such as progressive human immunodeficiency virus (HIV) infection and its associated opportunistic complications.
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PMID:Reversal of ferritin-mediated immunosuppression by levamisole: a rationale for its application to management of the acquired immune deficiency syndrome (AIDS). 759 11

Human placental ferritin is an immunosuppressive protein composed of a 43-kDa subunit (p43) and ferritin light chains. Its physiological action seems to be downregulation of the immune response of the mother against her embryo. Elevated levels of p43 in serum are associated with pregnancy, lymphomas, breast cancer, and AIDS. Although it is known that p43 is produced by activated T lymphocytes, the specific T-lymphocyte subset involved is unknown. p43 is measured by enzyme-linked immunosorbent assays with CM-H-9 monoclonal antibody specific for p43. We studied the de novo biosynthesis of p43 by isolated activated CD4+ and CD8+ T lymphocytes in a normal donor and in a patient with elevated levels of p43 in serum. The results indicated that p43 was synthesized by activated CD4+ lymphocytes from the normal donor (0.45% of the total de novo proteins) but that its biosynthesis by CD8+ lymphocytes was below the level of detection. The activated CD4+ lymphocytes from the patient with elevated levels of p43 in serum overproduced p43 (3.8% of the nascent proteins). Since it was shown that a subset of CD8+ lymphocytes has receptors for p43, the latter may be considered an immunoregulatory cytokine produced mainly by activated CD4+ lymphocytes.
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PMID:The immunosuppressive human placental ferritin subunit p43 is produced by activated CD4+ lymphocytes. 769 33

We report a high prevalence of elevated serum and red cell ferritin (SF and RCF) levels in 168 patients with HIV infection. SF levels increase with clinical worsening of infection and with decreasing CD4+ lymphocyte counts (ANOVA, p < 0.001) while RCF is significantly higher in asymptomatic AIDS patients (ANOVA, p < 0.001) and in those treated with zidovudine (AZT) (ANOVA, p < 0.001). It is suggested that, although inflammatory processes may explain high SF levels, if we also take in account RCF levels a possible association between iron overload and HIV infection might exist, and this may be worsened by AZT treatment. The significance of these high ferritin levels and their effects on immune system suppression and susceptibility to infectious and neoplastic complications in these patients merits further investigation.
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PMID:Prevalence of high serum and red cell ferritin levels in HIV-infected patients. 806 64


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