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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The non-obese diabetic mouse (NOD mouse) is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta cells mediated by T cells and culminating in insulin-dependent diabetes mellitus. Here, we report that the NOD mouse also develops Coombs'-positive hemolytic anemia, a B cell-mediated autoimmune disease. Aged NOD mice were found to have splenomegaly and jaundice predominantly due to raised unconjugated serum bilirubin. Their hematocrits were markedly lowered, and there was a reciprocal increase in the reticulocyte count. Red blood cells (RBC) from anemic mice showed a normal lytic response to hypotonicity. RBC from non-anemic mice had normal half lives in non-anemic, non-diabetic NOD mice by 51Cr labeling but, dramatically shortened half lives in anemic mice. Similar results were obtained with RBC from anemic mice. Hemolysis could be transferred with serum from anemic mice resulting in reticulocytosis. The antibody-mediated nature of the anemia was confirmed with the direct Coombs' test. Anemia was found only in mice aged greater than 200 days and was more common in diabetic (4/8) than non-diabetic (1/16) mice at 300 days. However, by 550 days, 14/17 non-diabetic mice were affected.
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PMID:Hemolytic anemia in non-obese diabetic mice. 188 56

The ability of vitamin E (alpha-tocopherol) to stimulate erythroid progenitor cells was investigated in an attempt to identify ways to ameliorate zidovudine (azidothymidine, AZT)-induced anemia. In vitro, alpha-tocopherol acid succinate (ATS), upon incubation with murine bone marrow cells at concentrations of up to 4 micrograms/ml, caused a dose-dependent increase in erythroid colony-forming unit (CFU-E)-derived colonies. This increase was equivalent to the effect demonstrated by 50 mU of recombinant human erythropoietin (rhEpo) or 200 U of recombinant interleukin 3 (rIL-3). For in vivo studies, anemia was produced in CD-1 male mice by administering AZT in drinking water (1.5 mg/ml). Treatment with vitamin E (50 mg/kg body weight) or Epo (0.4 U per mouse) was initiated 24 h later and continued for five consecutive days. Seventh day bone marrow cells from femurs were assayed for CFU-E-derived colonies. Both vitamin E and Epo significantly increased the number of CFU-E-derived colonies by 75% and 86% of control, respectively, indicating that these agents were approximately similar in protecting the bone marrow from AZT-induced toxicity.
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PMID:Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E. 189 52

The effect of an ethanolic extract of the plant Trianthema portulacastrum L. on the CCl4-induced chronic hepatocellular damage of Swiss albino mice has been investigated. The normal mice received olive oil (0.2 ml/mouse) for five weeks. The CCl4 control mice, on the other hand, received CCl4 (0.05 ml/mouse) in olive oil for five weeks. The extract was administered at the dose of 100 mg/kg or 150 mg/kg for five weeks by gastric intubation in addition to CCl4 treatment. The CCl4 administration alone caused hepatocellular necrosis, severe anemia, leucopaenia, lymphocytopaenia, neutrophilia, eosinophilia and haemoglobinaemia along with the alterations of plasma albumin and globulin. The administration of plant extract (at 100 or 150 mg/kg) restored the CCl4-induced alterations of the haematological parameters to the normal level. The extract of T. portulacastrum elicited a marked protection against CCl4-induced hepatotoxicity as indicated by the several haematological parameters, related indices of formed elements, and different fractions of plasma protein. We also observed the dose-dependent antihepatotoxic effect of the extraction on these mice. The 150 mg/kg of extract was found to be more effective in normalizing the toxic effects of CCl4 on the above parameters of mice. These results suggest that the hepatoprotective effect of T. portulacastrum could be caused by its critical involvement in modulating several factors associated with erythropoiesis, and the boosting of general immunity of the host.
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PMID:Antihepatotoxic potential of Trianthema portulacastrum in carbon tetrachloride-induced chronic hepatocellular injury in mice: reflection in haematological, histological and biochemical characteristics. 987 35

The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P <.001) but have a normal hematocrit (Hct) (approximately.47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)), and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P <.01). In response to EPO, the Hct of the GATA-1(low) mice raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by the controls (P <.01). Both the GATA-1(low) and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1(low) mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen.
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PMID:Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice). 1134 29

In man, chloramphenicol (CAP), induces two major haemotoxic effects. First, a reversible, dose-related reticulocytopenia and anaemia developing during treatment. Second, a non-dose-related aplastic anaemia (AA), developing weeks after treatment, is often irreversible and fatal. In previous studies, we developed a mouse model of the reversible reticulocytopenia/anaemia using CAP succinate (CAPS); attempts to induce AA in the mouse with CAPS were unsuccessful; in the rat, CAPS induced only minimal haemotoxicity. We therefore wished to investigate haematological changes caused by CAPS in a third rodent, particularly in relation to the induction of significant 'late stage' bone marrow depression (AA). Female guinea pigs were gavaged with CAPS in three experiments. In a dose ranging study, CAPS (at 2500 and 3500 mg/kg) was administered daily for 9 days, and blood examined at 1 day post dosing. CAPS induced increased erythrocyte values (an apparent haemoconcentration effect), and reduced reticulocytes and femoral marrow nucleated cell counts (FNCC). In a second experiment, CAPS was given at 333, 666 and 1000 mg/kg (13 days); haematological changes were compared with results from the initial study, with evidence of dose-related effects. In a final experiment, CAPS was administered (825 mg/kg, 16 days) and blood studied at 1, 12, 28 and 63 days post dosing. At day 1, erythrocyte values were decreased (NS), and reticulocytes and FNCC were reduced; the marrow was hypocellular with erythroid depletion. At 12 and 28 days, values returned towards the normal range. At 63 days, parameters were normal. Thus, CAPS (825 mg/kg for 16 days) induced changes comparable to the reversible bone marrow depression seen in man; but there was no evidence of 'late stage' (i.e. at 63 days) marrow depression, as would be seen in a developing or overt marrow aplasia (AA). The guinea pig (like the mouse) is a model for the early events, but is not a good model for CAP-induced AA in man.
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PMID:Studies on the haemotoxicity of chloramphenicol succinate in the Dunkin Hartley guinea pig. 1264 19

The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia of inflammation (AI). We examined the acute and chronic effects of hepcidin in the mouse. Injections of human hepcidin (50 microg/mouse), but not of its diluent, induced hypoferremia within 4 hours. To examine the chronic effects of hepcidin, we implanted either tumor xenografts engineered to overexpress human hepcidin or control tumor xenografts into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with hepcidin-producing tumors developed more severe anemia, lower serum iron, and increased hepatic iron compared with mice with control tumors. Hepcidin contributes to AI by shunting iron away from erythropoiesis and sequestering it in the liver, predominantly in hepatocytes.
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PMID:Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. 1547 21

Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an anti-neoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.
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PMID:Erythropoietin enhances immune responses in mice. 1750 33

The purpose of the present study was to investigate the efficacy of a liquid culture filtrates of the entomogenous fungus Paecilomyces tenuipes (PTCF) and its main active glycoprotein-enriched (PGF) fraction against hematotoxicity in mice treated with 5-fluorouracil (5-FU). Oral administration of PTCF (100 mg/kg/d) for 7 consecutive days after 5-FU injection significantly suppressed reductions in the red and white blood cell counts in peripheral blood, and accelerated their recoveries. From PTCF, glycoprotein-enriched fraction (PGF, >90% protein, approximately 15 kDa determined by SDS-PAGE) was separated as active ingredient that ameliorates 5-FU-induced anemia. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of trypsinized-PGF showed 11 fragment ion peaks. Effective recoveries of erythrocytopenia and leukocytopenia were observed when PGF was co-administered with murine recombinant erythropoietin (mrEPO; 5 U/mouse). Oral administration of PGF also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 12, and markedly hastened their recoveries on day 20, in dose-dependent manners. Reductions in erythroid progenitor colonies, such as colony-forming units (CFU)-erythroid and burst-forming units-erythroid mix, formed by bone marrow cells from 5-FU-treated mice were markedly improved by oral administration of PGF with subcutaneous mrEPO. Oral administration of PGF also increased the myeloid lineage progenitor, CFU-granulocyte-macrophages, in cultured bone marrow cells. These findings suggest that PGF isolated from P. tenuipes has the potential to protect against 5-FU-inudced erythrocytopenia and leukopenia, especially in combination with mrEPO, and also has hematopoietic activity, through stimulation of immature erythroid as well as myeloid progenitor cell differentiation.
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PMID:The liquid culture filtrates of entomogenous fungus Paecilomyces tenuipes and its glycoprotein constituent protects against anemia in mice treated with 5-fluorouracil. 1867 90

The first mature cells to arise in the developing mammalian embryo belong to the erythroid lineage. This highlights the immediacy of the need for red blood cells during embryogenesis and for survival. Linked with this pressure is the necessity of the embryo to obtain and transport iron, synthesize hemoglobin, and then dispose of the potentially toxic heme via the stress-induced protein heme oxygenase-1 (HO-1, encoded by Hmox1 in the mouse). Null mutation of Hmox1 results in significant embryonic mortality as well as anemia and defective iron recycling. Here, we discuss the interrelated nature of this critical enzyme with iron trafficking, erythroid cell function, and embryonic survival.
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PMID:Heme Oxygenase-1: A Critical Link between Iron Metabolism, Erythropoiesis, and Development. 2216 89

N,N-dimethyl-p-toluidine was nominated for toxicology and carcinogenesis studies by the National Cancer Institute based on the potential for human exposure through its use in dental materials and bone cements and the lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1/N mice were administered N,N-dimethyl-p-toluidine (greater than 99% pure) in corn oil by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, mouse peripheral blood, and mouse and rat liver. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses, 5 days per week for 25 days. On day 88, blood was collected from core study rats for hemoglobin and methemoglobin analyses only. All 1,000 mg/kg male and female rats and one 500 mg/kg male rat died by study day 3. Mean body weights of all surviving dosed groups of males and females were significantly less than those of the vehicle controls. Clinical findings associated with exposure to N,N-dimethyl-p-toluidine included cyanosis, abnormal breathing, and lethargy in groups administered 250 mg/kg or greater. Methemoglobinemia appeared to be the primary hematologic toxic response, and many other lesions could be explained as secondary to methemoglobin formation including Heinz body formation; a macrocytic, hypochromic, responsive anemia; and increased hematopoietic cell proliferation in the spleen and bone marrow. In general, hematologic changes were dose-related and occurred at both evaluated timepoints in all dosed groups. Anemia was evidenced by decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts; erythrocyte macrocytosis was characterized by increases in mean cell volume and mean cell hemoglobin values; erythrocyte hypochromia was evidenced by decreases in mean cell hemoglobin concentration values; and an erythropoietic response to the anemia was characterized by substantially increased reticulocyte and nucleated erythrocyte counts. Liver weights of all surviving dosed groups of males and females were significantly greater than those of the vehicle controls. Kidney weights of all surviving dosed groups of females were significantly greater than those of the vehicle controls. There were significant decreases in left cauda epididymis and left epididymis weights in 250 mg/kg males. There was a dose-related decrease in the number of cycling females, with only four females in the 250 mg/kg group having regular cycles and females in the 125 and 250 mg/kg groups spending a significantly higher proportion of time in extended diestrus compared to the vehicle control group. In the surviving groups of rats, there were significantly increased incidences of pigmentation in the liver of all dosed groups, hepatocyte hypertrophy in groups administered 125 mg/kg or greater, and hepatocyte necrosis in 62.5, 250, and 500 mg/kg females. In the olfactory epithelium of the nose, there were dose-related increases in the incidences and severities of degeneration in all dosed groups and significantly increased incidences of metaplasia in the 250 and 500 mg/kg groups. In the respiratory epithelium of the nose, there were significantly increased incidences of hyperplasia and squamous metaplasia in all of the groups administered 125 mg/kg or greater. The incidences of glandular hyperplasia of the nose were significantly increased in males and females administered 125, 250, or 500 mg/kg. In the spleen, there were significantly increased incidences of capsule fibrosis, congestion, mesothelial hypertrophy, and lymphoid follicle atrophy primarily in groups administered 125 mg/kg or greater. Hematopoietic cell proliferation and pigmentation were increased in severity in treated groups. In the kidney, there were significantly increased incidences of nephropathy (females), pigmentation (males and females), papillary necrosis (males and females), and mineralization (males). Other treatment-related lesions included inflammation of the forestomach in males, mesenteric lymph node atrophy in females, and bone marrow hyperplasia in males and females. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 15, 30, 60, 125, or 250 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All 250 mg/kg male and female mice (except for one male mouse) died before day 10, and three males and two females administered 125 mg/kg died before the end of the study. The final mean body weight of 125 mg/kg males and the mean body weight gains of 125 mg/kg males and females were significantly less than those of the vehicle controls. Clinical findings associated with administration of N,N-dimethyl-p-toluidine included abnormal breathing, thinness, lethargy, cyanosis, and ruffled fur in 125 and 250 mg/kg males and females. Methemoglobinemia appeared to be the primary hematologic toxic response; however there were less severe erythron changes compared to the 3-month study in rats. In females, no erythron changes were detected up to 125 mg/kg. In males, inconsistent and minor decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts, and increased reticulocyte counts occurred in groups administered 60 mg/kg or greater. Methemoglobin values were minimally increased in males and females administered 30 mg/kg or greater. Heinz bodies were slightly increased in 60 mg/kg females, 125 mg/kg males and females, and the one surviving 250 mg/kg male; Heinz body formation was considered secondary to methemoglobin formation. Liver weights of all dosed groups of mice were significantly greater than those of the vehicle controls. In the surviving groups of mice, there were significantly increased incidences of bronchiolar epithelium degeneration, bronchiolar epithelium regeneration, and peribronchiolar chronic active inflammation in the lung of 125 mg/kg groups, and histiocytic infiltrates of the alveoli in 125 mg/kg females. In the nose, there were significantly increased incidences of glandular hyperplasia and olfactory epithelium metaplasia in the 125 mg/kg groups and olfactory epithelium degeneration in 60 mg/kg females and 125 mg/kg males and females. In the thymus, the incidences of thymocyte necrosis in the 125 mg/kg groups were significantly increased. In the liver, the severities of cytoplasmic vacuolization of the hepatocytes were increased in dosed groups of males and females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered 0, 6, 20, or 60 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 104 or 105 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses for 86 days. Survival of 60 mg/kg males was significantly less than that of the vehicle controls. Mean body weights of 60 mg/kg males and females were more than 10% less than those of the vehicle controls after week 61 and week 33, respectively. Clinical findings included signs of pallor in 60 mg/kg females and hyperactivity and boxing behavior in 20 mg/kg females and 60 mg/kg males and females. The hematology findings at the 3-month timepoint were consistent with those in the 3-month study in rats which indicated that methemoglobinemia was the primary hematologic toxic response. In the 20 and 60 mg/kg groups, there were dose-related decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts. There were similar trends toward erythrocyte macrocytosis and hypochromia and increased erythropoiesis as seen in the 3-month study. While the magnitudes of the erythron decreases were not sufficient to classify the responses as anemias, the patterns of the erythron changes were identical to those in the 3-month study. In the liver of 60 mg/kg males and females, there were significantly increased incidences of hepatocellular carcinoma and hepatocellular adenoma or hepatocellular carcinoma (combined). Numerous nonneoplastic liver lesions occurred in dosed males and females primarily in the 20 and 60 mg/kg groups. In the nose, there were significantly increased incidences of transitional epithelium adenoma and transitional epithelium adenoma or carcinoma (combined) in 60 mg/kg males; transitional epithelium adenoma also occurred in female rats administered 6 or 60 mg/kg. In the nose, there were significantly increased incidences of nonneoplastic lesions in the olfactory, respiratory, and transitional epithelia of dosed rats. These lesions occurred with the greatest incidence and severity in the 60 mg/kg groups. The incidences of inflammation and nerve atrophy were significantly increased in males and females administered 60 mg/kg. There were increased incidences of follicular cell adenoma or carcinoma (combined) of the thyroid gland in all dosed groups of males, and an increased incidence of follicular cell adenoma in 20 mg/kg females. In the spleen, there were significantly increased incidences of hematopoietic cell proliferation in all dosed groups of males and females. The incidences of congestion and mesothelial hypertrophy of the capsule were significantly increased in 60 mg/kg males and all dosed groups of females. There were also significantly increased incidences of capsular fibrosis and atrophy of the lymphoid follicle in the 60 mg/kg groups. The incidences of pigmentation were significantly increased in all dosed groups of males and in 60 mg/kg females. In all dosed groups of female rats, there were significantly increased incidences of nephropathy. (ABSTRACT TRUNCATED)
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PMID:Toxicology and carcinogenesis studies of N,N-dimethyl-p-toluidine (CAS No. 99-97-8) in F344/N rats and B6C3F1/N mice (gavage studies). 2302 99


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