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)

beta thalassemia (beta thal) in DBA/2J mice is a consequence of the spontaneous and complete deletion of the beta major globin gene. Homozygous beta thal mice have clinical and biological features similar to those observed in human beta thal intermedia. Erythrocytes in human beta thal are characterized by a relative cell dehydration and reduced K+ content. The role of this erythrocyte dehydration in the reduced erythrocyte survival, which typifies the disease, has not previously been evaluated. We examined for 1 month the effects on the anemia and the erythrocyte characteristics of beta thal mice of daily treatment with either clotrimazole (CLT), an inhibitor of red blood cell (RBC) dehydration via the Gardos channel, or human recombinant erythropoietin (r-HuEPO), or hydroxyurea (HU). The use of either r-HuEPO or HU induced a significant increase in hemoglobin (Hb), hematocrit (Hct), erythrocyte K+ and a decrease in percent reticulocytes, suggesting improved erythrocyte survival. CLT alone decreased only mean corpuscular hemoglobin concentration (MCHC) and cell density and increased cell K+. Thus, though the Gardos channel plays a major role in cell dehydration of murine beta thal erythrocyte survival. Combination therapy with r-HuEPO plus HU produced no incremental benefit beyond those of single drug therapy. However, addition of CLT to r-HuEPO, to HU, or to combined r-HuEPO plus HU led to statistically significant increase in Hb, Hct, and erythrocyte K+ compared with any of the regimens without CLT. These results suggest that CLT not only inhibits erythrocyte dehydration, but also potentiates the erythropoietic and cellular survival responses to r-HuEPO and HU.
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PMID:Combination therapy of erythropoietin, hydroxyurea, and clotrimazole in a beta thalassemic mouse: a model for human therapy. 856 46

In order to study the effects of acclimatization of Plasmodium in beta-thalassaemic mice, we used a mouse model of beta-thalassaemia (DBA/2J/beta-thal/beta-thal), similar to that observed in humans. We acclimatized 3 rodent malarias (P. berghei, P. chabaudi and P. yoelii) in DBA/2J and DBA/2J/beta-thal mice lines, by 4 intraperitoneal serial transfers. All 3 rodent malarias developed in red blood cells of beta-thalassaemic mice without losing their virulence. There was no delay in infection and peaks of parasitaemia were similar in beta-thalassaemic and normal mice. The mortality occurred earlier in beta-thalassaemic mice than in control mice for P. berghei and P. chabaudi. The difference was more pronounced for P. yoelii NS where normal mice did not die. These results could be explained by a failure of erythropoiesis in beta-thalassaemic mice, which are unable to compensate for the destruction of red blood cells by the parasites, and the mice died of anaemia. Ultrastructural examination of the rodent malaria parasites in beta-thalassaemic RBC showed a normal development even in the presence of Heinz bodies. In conclusion, no effective protection against malaria was provided by the beta-thalassaemia in this mouse model.
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PMID:The course of Plasmodium berghei, P. chabaudi and P. yoelii infections in beta-thalassaemic mice. 872 90

Our previous studies showed that the passage of the Friend virus complex through rats generated variant MuLVs, designated PVC111, PVC211, PVC321 and PVC441, that induced neurological disorders associated with tremor and paralysis. In this study, we tested the pathogenicity of four different PVC viruses in mice. Although histopathological studies revealed spongiform degeneration in the spinal cords of NFS mice infected with each PVC virus, only PVC441 frequently induced tremor and paralysis. After a long latency, all of these viruses induced leukemia associated with severe anemia. Further studies with PVC441 revealed dose- and age-dependence for tremor induction. In contrast to NFS mice, BALB/c, DBA/2 and C57BL/6 mice infected with PVC441 virus showed no neurological symptoms, although the virus could be isolated from the tissues of central nervous system. Despite the absence of neurological symptoms, a high degree of neuronal degeneration in the lumbar spinal cord was found in PVC441-infected BALB/c mice. A low degree of neuronal degeneration was found in PVC441-infected DBA/2 or C57BL/6 mice. Genetic crosses of these resistant mice with susceptible NFS mice indicated that resistance to tremor induction by PVC441 was dominant in all mouse strains and suggested that various host genes may control the susceptibility of mice to tremor induction by PVC441 virus.
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PMID:Factors affecting induction of neurological disorders in mice by paralysis-inducing Friend-related PVC viruses. 874 Dec 58

Malignant B-1 cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for the expansion of malignant B-1 cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-1 cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-1 malignant clones. In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically. IL-10 may enhance proliferation and the development of B-1 cell malignancy rather than antibody production by the B-1 cell subpopulation. Thus, IL-10 plays an important role in B-1 malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies.
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PMID:Requirement for increased IL-10 in the development of B-1 lymphoproliferative disease in a murine model of CLL. 887 29

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.
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PMID:Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb. 924 Dec 74

A 7 year old girl is described with congenital hypoplastic anaemia (Diamond-Blackfan anaemia, DBA) and an apparently balanced reciprocal translocation, 46,XX,t(X;19)(p21;q13). The girl has associated features including short stature, unilateral kidney hypoplasia, and a branchial cyst. Fluorescent in situ hybridisation (FISH) studies with 19q specific cosmids showed that the chromosome 19 breakpoint is located between the RYR1 and the XRCC11 loci spanning a physical region of 5 Mb. There is no family history of DBA and the parents and two healthy sibs have normal karyotypes. This is the first report of a balanced translocation associated with DBA and we suggest that the distinct phenotype has resulted from a de novo disruption of a functional gene. DBA can be inherited as an autosomal trait and our observation may indicate a candidate gene for the disorder in the 19q13 region.
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PMID:Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation. 932 70

Current therapy for several forms of anemia involves a weekly regime of multiple subcutaneous injections of recombinant human erythropoietin (hEpo). In an effort to provide a physiologically regulated administration of erythropoietin, we are developing cell lines genetically engineered to release hEpo as a function of oxygen tension. C2C12 cells were transfected using a vector containing the hEpo cDNA driven by the hypoxia-responsive promoter to the murine phosphoglycerate kinase gene. In vitro, these cells showed a threefold increase in hEpo secretion as oxygen levels were shifted from 21% to 1.3% oxygen. To test in vivo response, C2C12-hEpo cells were encapsulated in a microporous membrane and implanted subcutaneously on the dorsal flank of DBA/2J mice. On average, serum hEpo levels in animals exposed to 7% oxygen were two-fold higher than values seen in their control counterparts kept at 21% oxygen. Similar studies employing rats confirmed that hEpo delivery is regulated as a function of oxygen tension. These results suggest the feasibility of developing an oxygen-regulated, encapsulated cell-based system for hEpo delivery.
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PMID:A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension. 938 50

The transplantation of polymer encapsulated myoblasts genetically engineered to secrete erythropoietin (Epo) may obviate the need for repeated parenteral administration of recombinant Epo as a treatment for chronic renal failure, cancer or AIDS-associated anemia. To explore this possibility, the human and mouse Epo cDNAs under the control of the housekeeping mouse PGK-1 promoter were transfected into mouse C2C12 myoblasts, which can be terminally differentiated upon exposure to low serum-containing media. Pools releasing 150 IU human Epo per 10(6) cells per day and 390 IU mouse Epo per 10(6) cells per day were selected. Polyether-sulfone (PES) capsules loaded with approximately 200,000 transfected myoblasts from these pools were implanted on the dorsal flank of DBA/2J, C3H and C57BL/6 mice. With human Epo secreting capsules, only a transient increase in the hematocrit occurred in DBA/2J mice, whereas no significant response was detected in C3H or C57BL/6 mice. On the contrary, all mice implanted with capsules releasing mouse Epo increased their hematocrit over 85% as early as 7 days after implantation and sustained these levels for at least 80 days. All retrieved implants released Epo and contained well preserved myoblasts. Moreover most capsules were surrounded by a neovascularization. Mice transplanted with nonencapsulated C2C12 cells releasing mouse Epo showed only a transitory elevation of their hematocrit reflecting the poor engraftment of injected myoblasts. These results indicate that polymer encapsulation of genetically engineered myoblasts is a promising approach for the long-term delivery of bioactive molecules, allowing the resolution of the shortcomings of free myoblast transfer.
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PMID:Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts. 1032 23

The effect of trecrezan, a new immunoactive biostimulator, was studied in (C57BL/6 x DBA/2)F1 mice with immunodeficiency and anemia syndromes induced by a chronic guest-versus-host reaction. The drug combines immuno- and erythromodulant properties, being capable of eliminating anemia, decreasing the number of erythrokaryocytes and BFUs in bonemarrow of ill mice, and normalizing primary humoral immune response. Possible mechanisms of trecrezan action are discussed.
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PMID:[Immunopoiesis- and erythropoiesis-modulating properties of trecresan in experimental immune deficiency]. 1158 9

Exposure of hematopoietic progenitors to gamma irradiation induces p53-dependent apoptosis. However, host responses to DNA damage are not uniform and can be modified by various factors. Here, we report that a split low-dose total-body irradiation (TBI) (1.5 Gy twice) to the host causes prominent apoptosis in bone marrow cells of Friend leukemia virus (FLV)-infected C3H mice but not in those of FLV-infected DBA mice. In C3H mice, the apoptosis occurs rapidly and progressively in erythroid cells, leading to lethal host anemia, although treatment with FLV alone or TBI alone induced minimal apoptosis in bone marrow cells. A marked accumulation of P53 protein was demonstrated in bone marrow cells from FLV-infected C3H mice 12 h after treatment with TBI. Although a similar accumulation of P53 was also observed in bone marrow cells from FLV-infected DBA mice treated with TBI, the amount appeared to be parallel to that of mice treated with TBI alone and was much lower than that of FLV- plus TBI-treated C3H mice. To determine the association of p53 with the prominent enhancement of apoptosis in FLV- plus TBI-treated C3H mice, p53 knockout mice of the C3H background (C3H p53(-/-)) were infected with FLV and treated with TBI. As expected, p53 knockout mice exhibited a very low frequency of apoptosis in the bone marrow after treatment with FLV plus TBI. Further, C3H p53(-/-) --> C3H p53(+/+) bone marrow chimeric mice treated with FLV plus TBI survived even longer than the chimeras treated with FLV alone. These findings indicate that infection with FLV strongly enhances radiation-induced apoptotic cell death of hematopoietic cells in host animals and that the apoptosis occurs through a p53-associated signaling pathway, although the response was not uniform in different host strains.
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PMID:Friend leukemia virus infection enhances DNA damage-induced apoptosis of hematopoietic cells, causing lethal anemia in C3H hosts. 1209 91


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