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)

We have shown the possibility to modulate various anemic syndromes during acquired immunodeficiency differed in pathogenesis and induced by graft versus host reaction (GVHR). There are different variants of combined erythro- and immunopoiesis disorders in the semiallogeneic system DBA/2 --> B6D2F1: immunodeficiency plus hemolytic anemia and immunodeficiency plus hemolytic anemia plus immunocomplex glomerulonephritis. In the allogeneic system C57BL/6 --> BALB/c there is immunodeficiency plus hypoplastic anemia with reduced bone marrow erythropoiesis. Differences in pathogenesis of anemic syndrome are connected with the functional properties of macrophages and cytokine production by macrophages. There is some positive effect of chronic hypoxia on GVHR-induced immunopathology in B6D2F1 mice: it increases humoral immune response, has favorable effect on anemia and corrects early and late committed precursor number. The absence of any influence of chronic hypoxia on the secreted activity of macrophages gives an evidence to the direct influence of erythron on the humoral immune response. VM-2-84 has favorable effect on anemia (suppresses IL-1 production, reduces the number of early erythroid precursors and stimulates the amount of the granulocyte and macrophage precursors) in B6D2F1 mice with glomerulonephritis. The compound from alkancarboxylic acids - VM-2-84, up to two months decreases proteinuria and reduces proliferation of mezangiocytes and chronic inflammation with the restoration of immune system. Trecrezan, while having beneficial effect on anemia, reduces a hyperplasia of erythron in mice with immunodeficiency; it influences the production of monokines. The obtained facts about effectiveness of preparation possessing combined erythro- and immunopoiesis-modulating properties, open new ways of a target regulation of disorders of immunity.
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PMID:The Correction of Combined Immuno- and Hemopoiesis Disorders Induced by Graft-Versus-Host Reaction. 1268 18

In an effort to understand what limits the virulence of malaria parasites, we infected inbred mice of three genotypes (C57Bl/6J, CBA/Ca and DBA/2) with one of two parasite lines of the rodent malaria Plasmodium chabaudi. One of these parasite lines had been serially passaged through C57Bl/6J mice and had evolved higher asexual growth rate, virulence and transmission in the process. The other parasite line was the unadapted ancestral line which had low virulence. In all three host genotypes, the C57Bl/6J-adapted parasite line was more virulent than the ancestral line thus indicating that trade-offs in virulence between alternative host genotypes had not placed strong constraints on the evolution of high virulence in this system. By examining the infection dynamics for fitness-related components-asexual parasite population growth, transmission and virulence-we revealed alternative possible explanations for what sets the upper limit to virulence in nature. The total number of transmission forms (gametocytes) produced during the infection, a measure of parasite Darwinian fitness, was four-fold higher in mice that survived the infection than those which died. Among mice that survived, total gametocyte production was greatest in the host genotype that suffered intermediate levels of morbidity (anaemia and weight loss). Thus, there were transmission costs of high virulence that were partly due to host death (as most theoretical models of virulence evolution assume), but perhaps partly due to some factor related to high morbidity. Both mortality and morbidity-related factors might therefore influence the upper limit on virulence of malaria parasites.
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PMID:Virulence in rodent malaria: host genotype by parasite genotype interactions. 1279 7

All mice harboring the X-linked Gata1low mutation in a predominantly CD1 background are born anemic and thrombocytopenic. They recover from anemia at 1 month of age but remain thrombocytopenic all their life and develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, at 12 months. The effects of the genetic background on the myelofibrosis developed by Gata1low mice was assessed by introducing the mutation, by standard genetic approaches, in the C57BL/6 and DBA/2 backgrounds and by analyzing the phenotype of the different mutants at 12 to 13 (by histology) and 16 to 20 (by cytofluorimetry) months of age. Although all the Gata1low mice developed fibrosis at 12 to 13 months, variegations were observed in the severity of the phenotype expressed by mutants of different backgrounds. In C57BL/6 mice, the mutation was no longer inherited in a Mendelian fashion, and fibrosis was associated with massive osteosclerosis. Instead, DBA/2 mutants, although severely anemic, expressed limited fibrosis and osteosclerosis and did not present tear-drop poikilocytes in blood or extramedullary hemopoiesis in liver up to 20 months of age. We propose that the variegation in myelofibrosis expressed by Gata1low mutants of different strains might represent a model to study the variability of the clinical picture of the human disease.
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PMID:Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds. 1610 74

Iron homeostasis is one of the most critical functions in living systems. Too little iron can lead to anemia and tissue-specific disorders, such as splenomegaly. Excessive systemic iron is characteristic of hemochromatosis and is implicated in the brain in Parkinson's disease. With the exception of some single gene diseases like hemochromatosis, we know little about genetic-based, individual differences in iron-related parameters and their impact on biology. To model genetic control of iron homeostasis, we measured liver, spleen, and plasma iron concentrations, hematocrit and hemoglobin, transferrin saturation, and total iron-binding capacity in several BXD/Ty recombinant inbred mouse strains derived from C57BL/6 and DBA/2 progenitors. At 120 days of age, the animals were killed for iron analysis. All measures showed genetic-based variability consistent with polygenic influence. Analysis of principal components of the seven measures revealed three factors that we named availability, transport, and storage. Quantitative trait loci (QTL) analysis revealed one suggestive QTL on chromosome 5 for availability, two suggestive QTL (one on chromosome 1 and the other on chromosome 7) for transport, and one weak QTL on chromosome 2 for storage. The results show that iron homeostasis is a complex trait and is influenced by multiple genes.
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PMID:Systems genetic analysis of peripheral iron parameters in the mouse. 1747 78

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3% of all leukemias in adults. The skin lesions were described in about 10-12% of patients. Vasculitis in lymphoproliferative disease is relatively uncommon and may predate the diagnosis of lymphoproliferative disease. A 54-year old female with one month history of general symptoms and sudden onset of maculopapular exanthema on the skin, suffered from anemia, leukopenia and thrombocytopenia. Examination of the skin biopsy revealed lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44 antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow and of the peripheral blood cells that revealed pathological cell population with expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with a single dose of cladribrine. The patient with acute vasculitis should be screened and monitored for possible lymphoproliferative diseases. Skin manifestation of acute vasculitis accompanied with hairy cells may be the first manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the first line of therapy for HCL and induces a total response in more than 80% of cases with HCL.
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PMID:Paraneoplastic vasculitis associated with hairy cell leukemia. 1909 93

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) belong to the interleukin-6 family of cytokines. The authors' previous in vitro work demonstrated that in mouse cells mouse OSM (mOSM) signals through a heterodimeric receptor complex incorporating the mOSM-specific receptor mOSMRbeta while human OSM (hOSM) and bovine OSM (bOSM) use the mouse LIF receptor mLIFRbeta rather than mOSMRbeta. These in vitro data suggest that prior studies in mouse systems with hOSM or bOSM (the usual molecules used in early studies) reflect LIF rather than OSM biology. The current work assessed whether or not this divergence in actions among these three OSMs also occurs in vivo in mouse models. Adult female (C57BL/6J x DBA/2J) F(1) mice were engineered to stably overexpress mOSM, hOSM, or bOSM by retrovirus-mediated gene transfer (n = 10 or more per group). After 4 weeks, molecular and hematologic profiles and anatomic phenotypes in multiple organs were assessed by standard techniques. Animals overexpressing either hOSM or bOSM had an identical phenotype resembling that associated with LIF activation, including significant hematologic abnormalities (anemia, neutrophilia, lymphopenia, eosinopenia, and thrombocytosis); weight loss; profound enlargement (lymph node, spleen) and/or structural reorganization (lymph node, spleen, thymus) of lymphoid organs; and severe osteosclerosis. In contrast, mice overexpressing mOSM did not develop hematologic changes, weight loss, or osteosclerosis and exhibited more modest and anatomically distinct restructuring of lymphoid organs. These data indicate that activities imputed to OSM and the mOSMRbeta signaling pathway using in vitro and in vivo mouse experimental systems are unique to mOSM.
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PMID:Mice overexpressing murine oncostatin M (OSM) exhibit changes in hematopoietic and other organs that are distinct from those of mice overexpressing human OSM or bovine OSM. 1911 26

Cerebral malaria (CM) is a severe neurologic complication that arises predominantly in children and non-immune adults infected with Plasmodium falciparum. In the current study, the dynamics of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and pro- and anti-inflammatory cytokines were analyzed in P. berghei ANKA (P.bANKA)-infected C57BL/6, BALB/c, and DBA/2 mice. We showed that C57BL/6 mice were susceptible to CM, while BALB/c and DBA/2 mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The proportion and absolute numbers of Tregs in BALB/c and DBA/2 mice were significantly higher than in C57BL/6 mice. The levels of pro-inflammatory cytokines, such as IFN-gamma, TNF-alpha, IL-6, IL-17 and NO in CM-susceptible C57BL/6 mice were obviously higher than in CM-resistant BALB/c and DBA/2 mice, while the level of the anti-inflammatory cytokine IL-10 was the opposite to that of pro-inflammatory cytokines, confirming that an appropriate balance between pro- and anti-inflammatory immune responses is essential to control the pathogenesis of severe malaria, and Tregs are important regulators if this balance is to be maintained. In vivo depletion of Tregs significantly protected C57BL/6 mice from experimental CM and the production of pro- and anti-inflammatory cytokines was reversed, indicating that this cell population contributes to pathogenesis by modulating the balance of pro- and anti-inflammatory responses. Our data demonstrate that Tregs mediate the incidence and outcome of CM in P.bANKA-infected mice by modifying the pro-inflammatory response.
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PMID:Natural regulatory T cells mediate the development of cerebral malaria by modifying the pro-inflammatory response. 2021 95

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.
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PMID:VEGF promotes malaria-associated acute lung injury in mice. 2050 82

Iron homeostasis is crucial to many biological functions in nearly all organisms, with roles ranging from oxygen transport to immune function. Disruption of iron homeostasis may result in iron overload or iron deficiency. Iron deficiency may have severe consequences, including anemia or changes in immune or neurotransmitter systems. Here we report on the variability of phenotypic iron tissue loss and splenomegaly and the associated quantitative trait loci (QTLs), polymorphic areas in the mouse genome that may contain one or more genes that play a role in spleen iron concentration or spleen weight under each dietary treatment. Mice from 26 BXD/Ty recombinant inbred strains, including the parent C57BL/6 and DBA/2 strains, were randomly assigned to adequate iron or iron-deficient diets at weaning. After 120 days, splenomegaly was measured by spleen weight, and spleen iron was assessed using a modified spectrophotometry technique. QTL analyses and gene expression comparisons were then conducted using the WebQTL GeneNetwork. We observed wide, genetic-based variability in splenomegaly and spleen iron loss in BXD/Ty recombinant inbred strains fed an iron-deficient diet. Moreover, we identified several suggestive QTLs. Matching our QTLs with gene expression data from the spleen revealed candidate genes. Our work shows that individual differences in splenomegaly response to iron deficiency are influenced at least partly by genetic constitution. We propose mechanistic hypotheses by which splenomegaly may result from iron deficiency.
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PMID:Genetic analysis of iron-deficiency effects on the mouse spleen. 2173 93

This study was designed to investigate the children with congenital (Diamond-Blackfan Anaemia - DBA) and acquired pure red cell aplasia (PRCA). 4 children, aged 1 month to 3 years with PRCA were enrolled in a trial. Investigations include: detailed history and physical examination, complete blood count with red blood cell indices, reticulocyte count, bone marrow examination, iron metabolism, viral serologies, immunological and urine analysis, anti-erythrocyte antibodies, measurement of hemoglobin F and erythrocyte adenosinedezaminase activity, chest x-ray, liver and renal function tests. Based on clinical and para-clinical data analyses and catamnestic observations two cases were diagnosed with DBA and other two with acquired PRCA among which one was determined by EBV virus and another by transient erythroblastopenia. Nowadays 3 children with PRCA are asymptomatic. In case of PRCA (because of its rare occurrence) a differentiated approach is required to every specific occasion. A series of investigations should be conducted to determine the origin and choose the treatment principles accordingly.
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PMID:[The pure red cell aplasia in children (observation 2010-2012 years)]. 2356 8


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