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

To determine whether release of tumor necrosis factor-alpha (TNF-alpha), a cytokine that affects iron homeostasis, may be selectively altered in hereditary hemochromatosis, we measured concentrations of TNF-alpha and interleukin-1 beta (IL-1 beta) in supernatants of cultured peripheral blood monocytes from 11 homozygotes for hereditary hemochromatosis, 11 healthy individuals, and five patients with iron-loading anemia. The gene for hereditary hemochromatosis is tightly linked to the HLA locus on chromosome 6, but its exact site and product are not known. The gene for TNF-alpha also is located within the HLA region. Monocytes were incubated from 4 to 36 hours in medium alone or with added lipopolysaccharide. Mean concentrations of immunoreactive TNF-alpha in supernatants were significantly lower for subjects with hereditary hemochromatosis as compared to healthy controls (P less than .037) and patients with iron-loading anemia (P less than .005); differences between homozygotes for hemochromatosis and healthy controls were up to 4.5-fold at 4 hours (P = .008), 1.9-fold at 12 hours (P = .036), and 7.0-fold at 36 hours (P = .001). Importantly, concentrations of IL-1 beta in supernatants were not significantly different among the three groups. We conclude that release of TNF-alpha by monocytes may be selectively impaired in hereditary hemochromatosis. Deficient activity of TNF-alpha may contribute to the disordered iron metabolism of this disease.
 ...
PMID:Decreased concentrations of tumor necrosis factor-alpha in supernatants of monocytes from homozygotes for hereditary hemochromatosis. 155 77

Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage.
 ...
PMID:Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis. 199 6

Weanling male CD-1 mice were fed low-iron or iron-supplemented diets for 31 days. Mice fed the low-iron diet exhibited typical signs of iron deficiency, which included reduced weight gains (P = 0.0041) and anemia (P less than 0.0001). The effect of iron deficiency on antibody production, lymphocyte blastogenesis, and sensitivity to endotoxin were evaluated. Antibody production against sheep red blood cells, a T-lymphocyte dependent response, was reduced in iron-deficient mice (P = 0.0067). In contrast, antibody production against dinitrophenyl-ficoll, a T-lymphocyte-independent response, was not affected by iron deficiency (P = 0.291). Iron deficiency reduced T-lymphocyte blastogenesis induced by concanavalin A (P = 0.011), but had no effect on B-lymphocyte blastogenesis induced by Escherichia coli lipopolysaccharide (P = 0.662). These results indicate that the immunosuppressive effects of iron deficiency are related to T-lymphocyte function associated with lymphocyte proliferation and antibody production. A significantly increased susceptibility to endotoxin, a T-lymphocyte-independent response involving nonspecific defense mechanisms, was not observed in iron-deficient mice. Mortality associated with endotoxin was 14.2% in the iron-deficient mice as compared to 35% in the iron-replete mice (P = 0.079).
 ...
PMID:The effect of iron deficiency on the immune response in mice. 307 54

Weanling female Swiss mice were fed copper-deficient or copper-replete diets for 28 days. Mice fed the copper-deficient diet exhibited typical signs copper deficiency, which included reduced weight gains, anemia, and low liver copper concentrations. The effect of copper deficiency on antibody production, in particular, T-lymphocyte dependent and independent antibody responses, lymphocyte blastogenesis, and sensitivity to endotoxin were evaluated. Antibody production against sheep red blood cells, a T-lymphocyte dependent response, was suppressed in copper-deficient mice (P less than .0001). In contrast, antibody production against dinitrophenyl-ficoll, a T-lymphocyte independent response was not altered by copper deficiency (P = 0.90). Lymphocyte blastogenesis studies demonstrated that copper deficiency did not alter T-lymphocyte blastogenesis induced by concanavalin A (P = 0.27) or B-lymphocyte blastogenesis induced by Escherichia coli lipopolysaccharide (P = 0.40). These results indicate that the immunosuppressive effects are not due to an impairment of lymphocyte blastogenesis, an intermediate step involved in the generation of an immune response, but rather are a manifestation of impaired T-lymphocyte function associated with antibody production. Increased susceptibility to endotoxin, involving nonspecific defense mechanisms, was also observed in copper-deficient mice. Mortality associated with the endotoxin was 68% in the copper-deficient mice as compared to 35% in the copper-replete mice (P = 0.0026). Impaired T-lymphocyte dependent antibody production and enhanced susceptibility to endotoxin were observed in copper-deficient mice exhibiting classical manifestations of copper deficiency.
 ...
PMID:The effect of copper deficiency on the immune response in mice. 330 Dec 53

Immune responses and hematologic alterations were investigated in splenectomized pigs after IM inoculation with Eperythrozoon suis. Early hematologic alterations were massive parasitism of RBC, severe hypoglycemia, moderate bilirubinemia, and mild anemia; later findings included severe anemia, minimal parasitism of RBC, spontaneous agglutination of RBC at 25 C and 4 C which was reversible at 37 C, transient thrombocytopenia, and mild bilirubinemia. The humoral immune responses consisting of a transitory hyperglobulinemia and increase of indirect hemagglutination (IHA) titers against E suis were attributed to immunoglobulin M cold agglutinins. Cell-mediated immune responses, measured by phytohemagglutinin- and pokeweed mitogen-induced lymphocyte blastogenesis, were reduced after massive parasitemia. Blastogenesis induced by Escherichia coli lipopolysaccharide mitogen was increased before the hyperglobulinemia and an increase in IHA titer. There was an increase in the uptake of [3H]thymidine by lymphocytes cultured without mitogens after the decline in total globulin concentration and IHA titer.
 ...
PMID:Experimental porcine eperythrozoonosis: T-lymphocyte suppression and misdirected immune responses. 387 72

We investigated the relationship between the increased cell diameter of Lyt-2+ T cells and the development of autoimmune disease in aging NZB and NZB X NZW F1 hybrid (BW) mice. Individual animals were analyzed for Lyt-2+ T cell size (by narrow-angle forward light scatter), anti-erythrocyte autoantibodies, anemia, proteinuria, and splenomegaly. The peak light scatter of the Lyt-2+ T cells correlated with the level of anti-erythrocyte autoantibodies and severity of hemolytic anemia, but not with proteinuria or splenomegaly. The cell size of this T cell subset did not increase in old BW or in NZB mice homozygous for the xid gene (NZB.xid). The in vivo administration of bacterial lipopolysaccharide to young NZB mice did not stimulate the enlargement of Lyt-2+ T cells. Ly-2+ T cells from old NZB mice could be stimulated by concanavalin A (Con A) to express interleukin 2 (IL 2) receptors and to synthesize DNA in vitro. However, in vivo administration of Con A to old NZB mice did not induce the expression of IL 2 receptors on Lyt-2+ T cells. Further, in vivo T suppressor function was impaired in old NZB mice with enlarged Lyt-2+ T cells. Thus, the enlargement of Lyt-2+ T cells in old NZB mice appears related to impaired T cell function in vivo and is associated with the development of anti-erythrocyte autoantibodies and autoimmune hemolytic anemia.
 ...
PMID:Enlargement of Lyt-2-positive T cells is associated with functional impairment and autoimmune hemolytic anemia in New Zealand Black mice. 392 48

Iron-deficiency anemia impaired the blastogenic response of splenic lymphocytes and partially purified T cells to Concanavalin A and phytohemagglutinin. The response of splenic lymphocytes and partially B cells to bacterial lipopolysaccharide was also significantly impaired. Caloric restriction in pair-fed mice did not have any significant effect. Blastogenic response to the three mitogens was restored to normal after anemic mice were fed the regular diet containing 25 to 30 mg Fe/kg (FeSO4) for approximately 10 days. We also found that in the anemic mice the mean wet weights per 100 g of body of spleen, heart, brain, and kidney increased, while those of the thymus and liver decreased. In the pair-fed mice only the mean wet weight of the liver significantly decreased. There was a small but significant decrease in the white blood count and peripheral lymphocyte count in the anemic but not the pair-fed mice. The mechanism by which iron deficiency impairs the cell-mediated immune response is discussed.
 ...
PMID:Impairment of blastogenic response of splenic lymphocytes from iron-deficient mice: in vivo repletion. 660 Mar 68

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor. 788 47

Transgenic mice carrying a modified human tumour necrosis factor (huTNF)/beta-globin gene construct linked to the T-cell-specific locus control region of the human CD2 gene express huTNF in their T cells which is released into the circulation and causes the development of a wasting syndrome. We now report that the mice develop anaemia, probably through enhanced erythrophagocytosis rather than inhibition of reticulocyte production. Thus autologous erythrocytes, as well as sheep erythrocytes, were cleared more rapidly from the circulation of transgenic mice than from littermate controls. By contrast, peritoneal macrophages from transgenic mice were less phagocytic in vitro than cells from controls. They also secreted less murine (mu)TNF when stimulated by either bacterial lipopolysaccharide or toxic malarial antigens. The yields of muTNF approached normal levels, however, when these refractory cells from the transgenic mice were stimulated in the presence of a high concentration of indomethacin, suggesting that the production of muTNF was inhibited by enhanced synthesis of prostaglandins. The parasitaemia of transgenic mice infected with Plasmodium yoelii was about 10-fold less at its peak than in controls, although it followed the same time-course, and the multiplication of P. chabaudi was inhibited to an even greater degree. This control of parasitaemia may also be explained by enhancement of macrophage activity, mediated by huTNF acting on the murine p55 receptor, presumably by increasing the removal of parasites by phagocytosis or their killing by toxic products released by the activated macrophages. These observations suggest that a factor in the anaemia of human malaria may be macrophage activation caused by the secretion of TNF that occurs in this disease.
 ...
PMID:Anaemia and resistance to malaria in transgenic mice expressing human tumour necrosis factor. 795 74

Proinflammatory cytokines play an important role in the pathogenesis of anemia in inflammatory diseases. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been reported to inhibit the synthesis of erythropoietin (EPO) in vitro. To evaluate the in vivo significance of this observation, we have investigated effects of the administration of bacterial lipopolysaccharide (LPS) and IL-1 beta on renal EPO production in rats. Measurements by competitive reverse-transcription polymerase chain reaction showed that EPO mRNA levels were significantly reduced in the kidneys of normoxic rats 6 h after the injection of LPS (0.1 or 1 mg/kg). In addition, LPS and IL-1 beta (1 microgram/kg) inhibited the increase in EPO mRNA and plasma EPO levels when administered to rats before hypoxia exposure (8% O2 in the inspiratory gas). Evidence for an inflammatory reaction in the kidneys of LPS-treated rats was provided by measurements of greatly elevated renal TNF-alpha mRNA levels. Furthermore, kidneys isolated from LPS-created rats produced less immunoreactive EPO when perfused hypoxically in vitro for 2 h. Thus mediators of the immune response inhibit renal EPO gene expression in vivo, which is relevant with respect to the impaired synthesis of EPO in inflammatory diseases in humans.
 ...
PMID:Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats. 932 87


1 2 3 4 5 6 7 Next >>