Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marrow aspirates from 11 patients with megaloblastic haemopoiesis and from 14 healthy individuals with normoblastic haemopoiesis were studied for antibodies associated with polychromatic/orthochromatic erythroblasts, using an 125I-labelled anti-human immunoglobulin reagent and autoradiography. In addition, the expression on these cells of receptors for FcIgG (FcR) and of the type I receptor for fragments of the third complement component (CR1) were investigated with receptor-specific monoclonal antibodies, 125I-labelled anti-mouse immunoglobulin and autoradiography. The percentages of immunoglobulin-positive erythroblasts were significantly greater in the megaloblastic than in the normoblastic marrows. Abnormally high percentages of labelled erythroblasts were present in patients without any manifestations of an autoimmune disorder. The percentage of labelled erythroblasts in the marrows of the patients correlated well with the degree of anaemia. FcR were absent on the majority of megaloblasts or normoblasts while the expression of CR1 was similar in both types of cell. The difference between the percentage labelling of megaloblasts and normoblasts was therefore unlikely to be due to greater binding of immune complexes with or without associated complement to megaloblasts than normoblasts. The megaloblast-bound immunoglobulin is, therefore, likely to have recognized abnormally expressed epitopes on the surface of megaloblasts. The results suggest that natural autoantibodies play a role in the destruction of erythroblasts during megaloblastic haemopoiesis.
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PMID:Natural autoantibodies may play a role in ineffective erythropoiesis during megaloblastic haemopoiesis. 182 31

Circulating immune complexes (CICs) are common in patients with the acquired immunodeficiency syndrome (AIDS) as in anemia. In our previous reports, we observed that the deposition of CICs on erythrocytes via C3b receptors (CR1) resulted in a defective CIC clearing system of erythrocytes and in high membrane osmotic fragility of such erythrocytes. We investigated the functional activity of erythrocyte CR1 in 89 patients with AIDS, 41 with AIDS related complex (ARC), 102 healthy homosexual volunteers, and 37 heterosexual males, in relation to the presence of CICs, antibody to lymphadenopathy associated virus/human T lymphotropic virus-III (LAV/HTLV-III), anemia, and the direct and indirect Coombs' tests. CICs were frequently found in all groups except heterosexual males. Absence of CR1 activity was observed in 85% of patients with AIDS, and in 59% with ARC. Impaired CR1 activity also occurred in the homosexual volunteer group. Positive direct Coombs' test and the presence of CICs correlated inversely with CR1 activity while a lowered hematocrit and the presence of antibody to LAV/HTLV-III correlated directly. Neither the sera nor the eluates from erythrocytes with a positive IgG Coombs' test contained IgG antibody against erythrocytes. This suggests decremental loss of CR1 activity progressing from asymptomatic LAV/HTLV-III antibody positive homosexual volunteers to the prodromal spectrum of ARC and finally progressing to a total disappearance in overt AIDS. Of 8 homosexuals volunteers demonstrating the composite of impaired CR1 activity, positive antibody to LAV/HTLV-III, and polyvalent positive direct Coombs' test (with gamma, mu, and C3b), all developed ARC or overt AIDS within 2 years of these observations.
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PMID:Hematologic correlates and the role of erythrocyte CR1 (C3b receptor) in the development of AIDS. 294 17

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.
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PMID:Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group. 984 84

Severe anemia is one of the most lethal complications in children infected with Plasmodium falciparum. The pathogenesis of this anemia is not completely understood. Experimental data from malaria-infected humans and animal models suggest that uninfected red cells have a shortened life span. This study looked for changes in the red cell surfaces of children with severe malarial anemia that could explain this accelerated destruction. A prospective case-control study was conducted of children with severe P falciparum anemia (hemoglobin of 5 g/dL or lower) admitted to a large general hospital in western Kenya. Children with severe anemia were compared with children who had symptoms of uncomplicated malaria and with asymptomatic children. Cytofluorometry was used to quantify in vitro erythrophagocytosis and to measure red cell surface immunoglobulin G (IgG) and the complement regulatory proteins CR1, CD55, and CD59. Red cells from patients with severe anemia were more susceptible to phagocytosis and also showed increased surface IgG and deficiencies in CR1 and CD55 compared with controls. Red cell surface CD59 was elevated in cases of severe anemia compared with asymptomatic controls but not as compared with symptomatic controls. The surface of red cells of children with severe P falciparum anemia is modified by the deposition of IgG and alterations in the levels of complement regulatory proteins. These changes could contribute to the accelerated destruction of red cells in these patients by mechanisms such as phagocytosis or complement-mediated lysis. (Blood. 2000;95:1481-1486)
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PMID:Red cell surface changes and erythrophagocytosis in children with severe plasmodium falciparum anemia. 1066 28

Severe anemia is one of the most lethal complications of Plasmodium falciparum malaria. Red blood cells (RBCs) from children with severe malarial anemia are deficient in complement regulatory proteins (CR1 and CD55). A case-control, age- and sex-matched study was carried out to determine whether these deficiencies are acquired or inherited and the relative contribution of these complement regulatory protein deficiencies, the immune complex level, and the parasite density to the development of severe malarial anemia. RBC CR1 and CD55 deficiencies resolved after treatment, suggesting that these changes were acquired. Using conditional logistic regression, a decline in CD55 (or CR1) (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.1-8.1; P<.001) and an increase in immune complex level (OR, 2.6; 95% CI, 1.5-4.8; P=.001) were significantly associated with severe malarial anemia.
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PMID:Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. 1255 40

Childhood malaria caused by Plasmodium falciparum is often characterized by severe anemia at low parasite burdens; the mechanism(s) responsible for this pathology remain to be defined. We have reported, based on clinical observations and in vitro models, that complement control proteins on erythrocytes such as CR1, the immune adherence receptor specific for C3b, may be reduced in childhood malaria, suggesting a possible role for complement in erythrocyte destruction. Intravascular lysis of iE by P. falciparum leads to release of erythrocyte breakdown products such as hemoglobin and hematin, which have inflammatory properties. In the present article, we demonstrate that in serum and in anticoagulated whole blood, moderate concentrations of hematin activate the alternative pathway of complement and promote deposition of C3 activation and breakdown products on erythrocytes. The degree of C3 fragment deposition is directly correlated with erythrocyte CR1 levels, and erythrocytes opsonized with large amounts of C3dg form rosettes with Raji cells, which express CR2, the C3dg receptor which is expressed on several types of B cells in the spleen. Thus, the reaction mediated by hematin promotes opsonization and possible clearance of the youngest (highest CR1) erythrocytes. A mAb specific for C3b, previously demonstrated to inhibit the alternative pathway of complement, completely blocks the C3 fragment deposition reaction. Use of this mAb in nonhuman primate models of malaria may provide insight into mechanisms of erythrocyte destruction and thus aid in the development of targeted therapies based on inhibiting the alternative pathway of complement.
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PMID:Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria. 1791 41

Plasmodium falciparum malaria causes 1-2 million deaths per year. Most deaths occur as a result of complications such as severe anemia and cerebral malaria (CM) (coma). Red cells of children with severe malaria-associated anemia (SMA) have acquired deficiencies in the complement regulatory proteins complement receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55). We investigated whether these deficiencies affect the ability of erythrocytes to bind immune complexes (ICs) and regulate complement activation. We recruited 75 children with SMA (Hb < or = 6 g/dL) from the holoendemic malaria region of the Lake Victoria basin, western Kenya, and 74 age- and gender-matched uncomplicated malaria controls. In addition, we recruited 32 children with CM and 52 age- and gender-matched controls. Deficiencies in red cell CR1 and CD55 in children with SMA were accompanied by a marked decline in IC binding capacity and increased C3b deposition in vivo and ex vivo. Importantly, these changes were specific because they were not seen in red cells of children with CM or their controls. These data suggest that the declines in red cell CR1 and CD55 seen in children with SMA are of physiologic significance and may predispose erythrocytes to complement-mediated damage and phagocytosis in vivo.
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PMID:Reduced immune complex binding capacity and increased complement susceptibility of red cells from children with severe malaria-associated anemia. 1831 66

Patients with systemic lupus erythematosus (SLE) have relative deficiencies of the C3b/C4b receptor (CR1, CD35) on erythrocytes (E). This receptor takes part in the binding, transport and endocytosis of circulating immune complex bound complement components (ICC). Besides the autoantibodies the abnormalities in IC elimination are fundamental to the pathogenesis of SLE. During the last 15 years more than 100 patients with SLE have been treated in our Department and their data on ICC clearance by ECR1 analyzed. After plasmapheresis the ECR1 expression and also the binding sites for ICC were increased, while the level of IC and autoantibodies were reduced. Stimulating erythropoiesis in patients with anaemia and lupus nephritis caused the decreased expression and functional activity of ECR1 to be improved. In patients with SLE the level of soluble CR1 was also decreased, but a significant portion of soluble CR1 bound ICC in vivo, especially in those with severe renal lesion.
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PMID:Immune complex clearance by complement receptor type 1 in SLE. 1860 99

In the present study, 12 patients with fever of undetermined origin, anemia and icterus were diagnosed with hemoplasma infection by light microscopy, transmission electron microscopy examination and PCR assay after being excluded from other usual febrile diseases. Complement receptor type I (CR1, CD35) expression on the surface of erythrocytes was assessed by flow cytometry using mouse anti-human CD35 antibody. Compared with healthy volunteers, the level of CD35 was significantly elevated in patients with severe hemoplasma infection at diagnosis, and decreased sharply after treatment. However, in latent infection cases without clinical manifestations, CD35 expression showed an ascending trend but had no statistical difference compared to the healthy controls. The present study demonstrated that hemoplasma infection can induce high levels of expression of CR1 on the membrane of red blood cells, which may be a reaction to the immunity challenge.
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PMID:Overexpression of complement receptor type I (CR1, CD35) on erythrocytes in patients with hemoplasma infection. 2064 10

The complement receptor 1 (CR1/CD35) protein acts as the major rosetting receptor in Plasmodium falciparum infection and several genetic variants of CR1 gene have been shown to be associated with quantitative expression of erythrocyte CR1 (E-CR1) level. However, CR1 level and gene polymorphisms exhibit differences in clinical manifestation of malaria in regions of varying disease endemicity. The result of the present study which analyzed three SNPs (intron 27 HindIIIA>T, exon 22 3650 A>G, and exon 33 5507 C>G) of the CR1 gene in Orissa, a hyperendemic state in eastern-India showed that a significantly increased risk for cerebral malaria (CM) was associated with AA genotype of both intron 27 and exon 22 when compared with mild, severe malaria anemia (SMA) and CM+SMA group respectively. Further, the overall haplotype analysis for all the three loci showed predominantly two major haplotypes 'AAC' coding for higher expression of CR1 and 'TGG' haplotype coding for low expression of CR1 level with the former haplotype being significantly associated with CM (P value<0.00619 after Bonferroni correction) compared to mild malaria. The 'TGG' haplotype was proportionately more in SMA cases compared to mild malaria though statistically not significant. These findings suggest that the mild malaria group had an intermediate level of E-CR1 and extremely low or high levels of CR1 can cause severity in malaria. Further large scale studies in different endemic regions are needed to explain the epidemiological differences between E-CR1 expression and clinical manifestation of malaria which may contribute to the understanding of malaria pathogenesis.
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PMID:High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India. 2095 Dec 38


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