Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The photosensitizing dye merocyanine 540 (MC 540) was evaluated as a means for purging malarially infected red cells from murine blood using the rodent malarial pathogens, Plasmodium yoelii and Plasmodium berghei, as models of human malaria. Malarially infected red cells bound more MC 540 and were more sensitive to MC 540-sensitized photoirradiation than were noninfected erythroid cells. Extracorporeal exposure of infected red cells to the dye and white light prevented the transmission of the disease in a transfusion model. P. berghei-infected red cells were more resistant to the antimalarial activity of MC 540 than were P. yoelii-infected cells, presumably because P. berghei preferentially infects reticulocytes whereas P. yoelii infects mature red cells. The possibility of using photoirradiation sensitized by MC 540 or related dyes to purge malarially infected donor blood is discussed.
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PMID:Evaluation of merocyanine 540-sensitized photoirradiation as a method for purging malarially infected red cells from blood. 203 97

Neutrophilia, monocytosis, eosinopenia and reactive lymphocytes were found in the peripheral blood of infants and children with acute malaria at presentation. These changes were mostly reversed by days 3 and 7 after starting treatment. Mild rebound eosinophilia was seen in three cases after starting treatment. In patients with low grade malaria and anaemia, peripheral blood counts did not alter significantly after treatment. Two patients with mild eosinophilia at presentation were subsequently found to have strongyloidiasis and the eosinophil count rose markedly in one after treatment of malaria. Bone marrows were hypercellular in all cases. There was a low mean percentage of myeloid precursors in the marrow of all children as compared with the normal. This was due to increased lymphocyte percentage in those with acute malaria and to marked erythroid hyperplasia in those with low grade malaria. Phagocytosis of parasitized and non-parasitized red cells by bone marrow macrophages was seen most frequently in children with high parasitaemias, but erythroblast phagocytosis was more commonly seen in those with low grade malaria. There was no absolute correlation between the presence or absence of erythrophagocytosis in marrow macrophages and the presence or absence of a positive direct antiglobulin test (DAT) in children with malaria. This indicates that immunological mechanisms cannot be implicated as the sole cause of erythrophagocytosis in these bone marrows.
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PMID:Peripheral blood and bone marrow leucocytes in Gambian children with malaria: numerical changes and evaluation of phagocytosis. 246 14

To study the cellular mechanisms involved in the ineffective erythropoiesis associated with malaria, an in vitro proliferative assay was used to measure the response to erythropoietin (Epo) of erythroid progenitor cells from malaria-infected mice. In this assay, spleen (SP) cells from phenylhydrazine (PHZ)-treated mice (PHZ-SP), enriched for erythroid progenitor cells, respond to Epo in a dose-dependent manner. Despite a similar degree of anemia, SP and bone marrow (BM) cells from Plasmodium berghei- or P. vinckei-infected mice did not show a significant response to Epo in this assay. When SP or BM cells from malaria-infected mice were added to cultures of SP or BM cells from PHZ-treated mice the response to Epo of these cells was significantly inhibited. Removal of parasitized red blood cells (pRBC) from SP cells of P. berghei-infected mice had no effect on the ability of the cells to inhibit the response to Epo. Adherent SP cells and SP cells positive for the Mac-1 antigen, from malaria-infected mice, were shown to be enriched for cells that could inhibit the response to Epo. Cell-free conditioned media (CM) prepared from SP cells of P. berghei- or P. vinckei-infected mice or from normal SP cells incubated with pRBC were also able to inhibit the response to Epo of SP cells from PHZ-treated mice. These investigations have shown that during the course of malaria infection, cells appear in the SP and BM capable of inhibiting, via soluble mediators, the response to Epo of erythroid progenitor cells. The cells responsible are probably macrophages. The nature of the factor(s) and its mechanism of action are not known. Through the ability to inhibit erythropoiesis, soluble factors may, in part, mediate the anemia associated with malaria.
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PMID:Inhibition of erythropoiesis by a soluble factor in murine malaria. 265 Nov 36

The anemia associated with malaria is complex, and multiple factors contribute to its severity. An increased destruction and a decreased production of erythrocytes are involved; however, the mechanisms responsible remain unclear. Tumor necrosis factor alpha (TNF-alpha), released by macrophages in response to infection, is thought to play a role through its ability to inhibit erythropoiesis. In these studies we have examined erythropoiesis in mice infected with Plasmodium berghei and in mice infused with recombinant TNF-alpha via implanted osmotic pumps. In both groups of mice there was (i) a reduction of pluripotent stem cells in the bone marrow and a concomitant increase in the spleen, (ii) a reduction of erythroid progenitor cells, and (iii) a reduced incorporation of 59Fe into erythrocytes. When P. berghei-infected mice were given antiserum against recombinant murine TNF, erythropoiesis was partially restored. There was a significant increase in bone marrow stem cells, erythroid progenitor cells, and 59Fe incorporation into erythrocytes in P. berghei-infected mice that had been treated with anti-TNF. How TNF may act, directly or indirectly, to inhibit erythropoiesis is not yet clear. These results demonstrate that TNF mediates, in part, the anemia associated with malaria.
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PMID:Tumor necrosis factor alpha and the anemia associated with murine malaria. 270 58

This work characterizes the erythropoietic interplay of the spleen, blood, and bone marrow in a lethal murine malaria, strain 17XL P. yoelii. This malaria runs a fulminant 7 day course in BALB/c/ByJ mice, marked by high levels of parasitized reticulocytes with death likely due to anemia. We have quantitated the levels of burst forming units-erythroid (BFU-E), the early, niche-seeking, largely erythropoietin-unresponsive erythropoietic precursors, and of colony forming units-erythroid (CFU-E), the more differentiated sessile erythropoietin-responsive precursors, in bone marrow, blood, and spleen, through the course of this malaria. A decline in marrow BFU-E began on day 2, but recovered, relatively, after day 3. Marrow cellularity declined, being but 75% normal on day 6. Spleen weight increased about 5-fold within 6 days with enlargement of erythroid, lymphoid, macrophage, and stromal compartments. Splenic BFU-E increased in the first 24 hr and 5-fold by day 6. Splenic CFU-E increased in the first 24 hr and into day 4. They then declined and showed a secondary, large-scale, sustained rise interrupted by death. Because the spleen was enlarging, a greater than 60-fold increase in the absolute number of splenic CFU-E occurred at the time of death. Marrow CFU-E followed the same pattern as splenic CFU-E, but the terminal increase represented but a 4-fold absolute increase because of declining marrow cellularity. High levels of erythropoietin occurred only late in the course of disease, likely in response to profound anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of splenic control of murine malaria: tissue culture studies of the erythropoietic interplay of spleen, bone marrow, and blood in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice. 277 62

There was a wide variation in the number of BFUe and CFUe in the bone marrow of Gambian children with falciparum malaria and moderate or severe anaemia. However, such children were often not deficient in these erythroid progenitors. The number of BFUe in patients who had parasitaemias greater than 1% was significantly lower than that in patients with parasitaemias less than 1%. There was also a statistically significant negative correlation between the number of BFUe and CFUe in the entire group of children studied. When autologous serum (30%, v/v) was used in the culture system, CFUe growth was observed even in the absence of added erythropoietin (EPO), indicating the presence of high levels of EPO or an EPO-like substance in the anaemic sera. It is concluded that children with Plasmodium falciparum malaria show no major abnormality in their erythroid progenitor cells and that the perturbation of erythropoiesis in such children occurs mainly in the morphologically recognizable erythroid precursor cells. The wide variation observed in the number of CFUe and BFUe in different patients, and the correlations between the number of BFUe and parasitaemia and the number of BFUe and CFUe are all probably largely related to the changing clinicopathological situation in patients with malaria and anaemia.
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PMID:A study of erythroid progenitor cells in the bone marrow of Gambian children with falciparum malaria. 328 94

Two hundred Hausa primigravidae at Zaria were divided into five groups in a randomized double-blind trial of antenatal oral antimalarial prophylaxis, and haematinic supplements. Group 1 received no active treatment. Groups 2 to 5 were given chloroquine 600 mg base once, followed by proguanil 100 mg per day. In addition, group 3 received iron 60 mg daily, group 4 folic acid 1 mg daily, and group 5 iron plus folic acid. Forty-five percent were anaemic (haemoglobin (Hb) less than 11.0 g dl-1) at first attendance before 24 weeks of gestation, and malaria parasitaemia (predominantly Plasmodium falciparum) was seen in 27%, of whom 60% were anaemic. The mean Hb fell during pregnancy in group 1, and seven patients in this group had to be removed from the trial and treated for severe anaemia (packed cell volume (PCV) less than 0.26). Only five patients in the other groups developed severe anaemia (P = 0.006), two of whom had malaria following failure to take treatment. Patients in group 1 had the lowest mean Hb at 28 and 36 weeks of gestation, and patients receiving antimalarials and iron (groups 3 and 5) had the highest Hb at 28 weeks, but differences were not significant, possibly due to removal from the trial of patients with severe anaemia. Anaemia (Hb less than 12.0 g dl-1) at six weeks after delivery was observed in 61% of those not receiving active treatment (group 1), in 39% of those protected against malaria but not receiving iron supplements (groups 2 and 4) and in only 18% of patients receiving both antimalarials and iron (groups 3 and 5). Folic acid had no significant effect on mean Hb. Proguanil was confirmed to be a highly effective causal prophylaxis. Prevention of malaria, without folic acid supplements, reduced the frequency of megaloblastic erythropoiesis from 56% to 25%. Folic acid supplements abolished megaloblastosis, except in three patients who were apparently not taking the treatment prescribed. Red cell folate (RCF) concentrations were higher in subjects with malaria, probably due to intracellular synthesis by plasmodia. Infants of mothers not receiving antimalarials appeared to have an erythroid hyperplasia. Maternal folate supplements raised infants' serum folate and RCF. Fourteen per cent had low birth weight (less than 2500 g), and the perinatal death rate was 11%; the greatest number were in group 1, but not significantly. A regime is proposed for the prevention of malaria, iron deficiency, folate deficiency and anaemia in pregnancy in the guinea savanna of Nigeria.
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PMID:The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria. 353 Jan 58

An impaired erythropoietic response to anemia has been noted in human patients with malaria and in rodents experimentally infected with Plasmodium berghei. We have attempted to characterize the erythropoietic response in mice with a fatal P berghei infection, with particular emphasis on changes in marrow hematopoietic stem cells. Mice infected with P berghei had dramatic decreases in bone marrow cellularity, erythroblasts, BFU-E, and CFU-E as early as 24 hours postinfection and before there was any change in hematocrit. With development of anemia, marrows became erythropoietic with some expansion of the CFU-E compartment, but the BFU-E pool remained depleted and reticulocyte response was inadequate. There was no significant change in CFU-S from marrows of malaria-infected mice one day after infection. The lethality of malaria infection may take three weeks to be revealed, but it may be determined within hours of the infection by the irreparable changes in marrow erythroid stem cells.
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PMID:Changes in hematopoietic stem cells in bone marrow of mice with Plasmodium berghei malaria. 390 19

Anemia is an important complication of P. falciparum malaria infection. This paper describes recent studies that have attempted to define some of the pathophysiological mechanisms involved in different forms of infection and at different stages of the illness. After an acute infection there is a steady fall in the haemoglobin level with an inappropriate reticulocyte response. Current evidence indicates that this form of anaemia may result from a combination of acute sequestration of iron in the reticuloendothelial system associated with a shortened red cell survival. Recent studies indicate that there may be a dyserythropietic component as well. The mechanism for the shortened red cell survival is uncertain; although it may be due in part to sequestration of parasitized cells, the haemoglobin level continues to fall for several weeks after the acute episode and other factors must be involved. The role of immune haemolysis appears to be relatively small. It is becoming apparent that severe dyserythropoiesis with minimal haemolysis plays a major role in the anaemias of Plasmodium falciparum infection, particularly in immune individuals. This phenomenon has been studied by both light and electron microscopy and by assessing the in vitro kinetics of erythroid precursor proliferation. The results indicate a major defect in erythroid maturation with a significant degree of erythrophagocytosis. Although these studies have provided a clearer picture of the pathophysiology of anaemia at different phases of P. falciparum infection, there is still little indication of how the basic changes in red cell production and survival are mediated.
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PMID:The anaemia of Plasmodium falciparum malaria. 634 Oct 4

The thalassemias are extremely heterogeneous in terms of their clinical severity, and their underlying pathophysiology relates directly to the extent of accumulation of excess unmatched globin chains: alpha in beta thalassemia and beta in the alpha thalassemias. However, the accumulation of each separate globin chain affects red cell membrane material properties and the state of red cell hydration very differently. These observations presumably account for the varying extent of ineffective erythropoiesis and peripheral blood hemolysis in the major variants of thalassemia. The thalassemias are a worldwide group of inherited disorders of globin-chain synthesis that developed in multiple geographic regions, probably because they provided partial protection against malaria. In normal assembly of adult hemoglobin (HbA-alpha 2 beta 2), alpha and beta globin are synthesized by genes on different chromosomes, whereas heme is synthesized primarily on mitochondria. The synthesis of these chains is very tightly coordinated so that the ratio of alpha globin to beta globin (beta in this case including the beta-like globins delta and gamma) is normally 1 +/- 0.05. Furthermore, specific erythroid proteases are designed to attack and destroy excess alpha or beta globin chains, demonstrating the deleterious impact of the accumulation of excess unmatched globin chains. In beta thalassemia, production of beta globin decreases and excess alpha globin accumulates. In alpha thalassemia, on the other hand, this process occurs in reverse. Perhaps in these disorders more than any others, molecular biologists have documented the deletional and transcriptional events leading to diminished synthesis of specific classes of globin chains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thalassemia: pathophysiology of red cell changes. 819 78


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