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)

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
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PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74

Despite intensified chemotherapy protocols, including autologous bone marrow transplantation (ABMT), stage IV neuroblastoma has a poor prognosis, and modern therapeutic trends are aimed at the eradication of minimal residual disease, which is though to be the main factor leading to relapse. In this pilot study, we report the systemic administration of high doses of interleukin-2 after ABMT in four patients. Five day cycles of IL-2 at a dose of 18 x 10(6) IU/m2/day were administered at variable time intervals as frequent as it was necessary to maintain the levels of natural killer (NK) cytotoxic activity higher than the median control value (40 LU/ml blood) throughout 1 year from the start of first IL-2 treatment. After IL-2 infusion, NK and LAK activities increased significantly (median 742 x 10(-3) LU/ml blood and 186.8 x 10(-3) LU/ml blood, respectively). Toxicities were transient and no life-threatening complications were observed. Fever, anorexia, skin rash and enlarged liver were always present. Anaemia, thrombocytopenia, leukocytosis, lymphocytosis and and eosinophilia occurred following most of the IL-2 courses. Although the small number of patients does not allow an estimation of the immunomodulatory-antineoplasic effects of IL-2, the results seem promising for the management of neuroblastoma patients.
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PMID:High-dose systemic interleukin-2 therapy in stage IV neuroblastoma for one year after autologous bone marrow transplantation: pilot study. 888 13

In a group of 70 patients with multiple myeloma (MM), formed by 25 patients examined while establishing the diagnosis and 45 patients examined in different stages of the disease, the authors evaluated the relationship of the bromodeoxyuridine "labelling index" (BrdUrd-LI) of myeloma plasma cells assessed by the method of double immunofluorescence (using antibody BU-1) and selected laboratory indicators of the disease. In the whole group the median and mean values of BrdUrd-LI of myeloma plasma cells were 2.0 (0.6-4.4%) and 2.1 +/- 0.9%, in the group of 25 patients examined during diagnosis it was 1.8 (0.6-4.1%) and 1.9 +/- 0.9%, in the group of 45 patients examined during different stages of MM it was 2.4 (0.6-4.4%) and 2.4 +/- 0.8%. Neither in the whole group nor in the sub-groups any statistically significant correlations were found between BrdUrd-LI values and the degree of anaemia, values of S-creatinine, S-MIG, S-albumin, S-B2M, S-ferritin, S-thymidine kinase, S-IL-6, S-IL-2, S-kIL-2R, the percentage ratio of myeloma plasma cells in bone marrow and the synthetic index of myeloma plasma cells paraprotein.
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PMID:[The bromodeoxyuridine index in multiple myeloma. I. Relation with selected laboratory indicators of the disease]. 892 21

Inbred CBA/J mice with chronic (20-week) Schistosoma mansoni infections demonstrate two distinct syndromes. Hypersplenomegaly syndrome (HSS), characterized by a massive spleen, liver fibrosis, ascites, and anemia, resembles hepatosplenic human schistosomiasis, complete with portal hypertension and shunting. Moderate splenomegaly (MSS) syndrome, with less severe pathology, parallels most chronic human infections. Phenotypic analyses of spleen cells for CD44, CD62L, CD45RB, Ia, and CD25 indicate that HSS mice have more activated and memory CD4+ T cells than do MSS mice. HSS animals also have more B cells that highly express B7-2. Anti-CD3 stimulated spleen cells from 8-week or chronically infected mice produce IL-4 and IL-10 in a manner that appears not to involve the CD28/B7-2 costimulation pathway. By contrast IFN-gamma production is augmented in the presence of anti-CD28 and decreased in the presence of anti-B7-2. Infected mice make very little IL-2 to anti-CD3, even with added anti-CD28. As cytokines affect resultant B-cell responses and HSS and MSS mice display distinctive isotypes, differential regulatory or anergy hypotheses may best explain MSS/HSS differences.
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PMID:Immunopathogenesis and immunoregulation in schistosomiasis. Distinct chronic pathologic syndromes in CBA/J mice. 899 59

We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or alpha-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+ cells in culture and interleukin (IL)-1alpha, IL-2, IL-4, tumor necrosis factor (TNF)alpha and soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+ and CD8+ T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+ and PCA1+ B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together. CD4+ T cells were reduced in number in 9 cases, while CD8+ T cells were reduced in 6 cases. The percentage of CD5+ B cells was increased in 5 cases. The percentage of PCA1+ cells was increased in all cases (mean +/- sd: 18 +/- 22 vs 0,2 +/- 1 in controls). The average PBL proliferative response to PHA was reduced (S.I. 71 +/- 55 vs 138 +/- 45 in controls) as well as that to PWM (S.I. 27 +/- 21 vs 75 +/- 24 in controls), despite IL-2 high levels, in all cases, in both sera (mean +/- sd: 648 +/- 351 pg/ml vs 16 +/- 4 pg/ml in controls) and culture supernatants (mean +/- sd: 1045 +/- 677 pg/ml vs 195 +/- 51 pg/ml in controls). In PHA stimulated cultures the percentage of CD25+ cells was reduced (mean +/- sd: 37 +/- 18 vs 63 +/- 14 in controls), sIL-2R levels were like controls in 7 cases. In sera sIL-2R levels were increased in all cases (mean +/- sd: 1256 +/- 465 U/ml vs 256 +/- 114 U/ml in controls), IL-1alpha was increased in all cases too, while IL-4 levels were increased only in 7 cases. Linear regression analysis generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels in supernatants of PHA stimulated culture as well as between S.I. and the percentage of CD25+ cells. Taken together these data suggest a state of B- and T-cell hyperactivation in AIHA. The low PBL proliferative response in vitro, explained in previous studies as a temporary functional exhaustion, might be itself a sign of the complete lymphocyte activation occurring in vivo in AIHA.
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PMID:Lymphocyte activation and cytokine production in autoimmune hemolytic anaemia (AIHA). 902 Apr 7

Until recently, chimpanzees were considered susceptible to human immunodeficiency virus type 1 (HIV-1) infection, but refractory to disease induction based on the asymptomatic status of all experimentally infected chimpanzees after over 10 years postinfection (PI). However, a decline in peripheral CD4+ T cells was noted in one chimpanzee (C499) of the Yerkes cohort of HIV-1 infected apes, after 11 years PI concurrent with increasing plasma viral load. These clinical signs were followed by the occurrence of opportunistic infections, thrombocytopenia, and progressive anemia leading to euthanasia. A second chimpanzee (C455) was transfused with blood from C499 collected during the symptomatic stage. Shortly thereafter, this second animal showed a rapid decline in peripheral CD4+ T-cell levels and sustained high viral load. Hematological analyses showed a 50% decrease in CFU-GM for both apes during the symptomatic phase and a reduction of 40% and 73% of the total CFU despite normal levels of CD34+ cells in the bone marrow. Cryopreserved sequential PBMC samples from these two chimpanzees were analyzed for constitutive and PHA-P induced levels of cytokines and chemokines. Data show that whereas there were no detectable constitutive levels of mRNA coding for IL-2, 4, and 10, there appears to be a transient increase in IFN-gamma message level coincident with increased viremia and this IFN-gamma synthesis decreased with disease progression. PHA-induced cytokine mRNA analysis showed low or undetectable levels of IL-4 and IL-10 mRNA in all samples and a marked decrease in the levels of IL-2 shortly after HIV infection. In addition, there was also a gradual decrease in IFN-gamma mRNA with progression of disease. Of interest were the findings of high to normal levels of PHA-induced synthesis of the chemokines MIP-1alpha, MIP-1beta, and RANTES in samples during the asymptomatic and early symptomatic period, which also dramatically decreased at late stages of the disease. These data suggest important roles for IL-2, IFN-gamma, and the chemokines in the regulation of immune responses in HIV-1-infected chimpanzees.
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PMID:Immune and hematopoietic parameters in HIV-1-infected chimpanzees during clinical progression toward AIDS. 927 Nov 84

Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndrome (HSS) while the rest present with moderate splenomegaly syndrome (MSS). HSS and MSS mice differ pathophysiologically (degree of splenomegaly, anaemia, ascites, periportal fibrosis, portal hypertension) and immunologically with regard to antibodies (idiotypic expression, isotype levels) to schistosome soluble egg antigens (SEA), and spleen cell phenotypic profiles. This study compared in vitro proliferative responses and IL-2, IFN gamma, IL-4, and IL-10 production by spleen cells from uninfected mice and mice with acute (8 wk), MSS or HSS schistosomiasis mansoni, upon exposure to anti-CD3 epsilon or SEA, Spleen cells from uninfected mice produce Il-2 to anti-CD3 epsilon but exposure of cells from all three groups of infected mice to anti-CD3 epsilon or SEA led to only very low levels of supernatant IL-2. Anti-CD3 epsilon- or SEA-stimulated production of IFN gamma or Il-4, and anti-CD3 epsilon-stimulated production of IL-10, displayed similar patterns: highest cytokine production by cells from mice with acute infections and lower levels of production that did not differ between the two chronic groups. In contrast, while SEA-stimulated IL-10 production was again highest with cells from mice with acute infections, spleen cells from mice with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a role in the immunoregulation that occurs in chronic schistosomiasis.
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PMID:IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. 929 93

Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and to determine how such abnormal activation might affect other cell lineages. Elevated levels of IgG, IgE and autoantibodies in IL-2R beta-/- mice were found to be associated with activated CD4+ T cells which secreted elevated levels of IL-4. Thymocytes in IL-2R beta-/- mice showed normal negative and positive selection patterns when analyzed in transgenic mice bearing a TCR specific for HY antigen, suggesting that neither IL-2 nor IL-15 is essential for thymic selection. Peripheral T cells in IL-2R beta-deficient mice underwent normal programmed cell death in response to staphylococcal enterotoxin B superantigen, in contrast to cells from mice deficient for either IL-2 or IL-2R alpha. Activated T cells in IL-2R beta-deficient mice expressed normal levels of Fas antigen and underwent normal apoptosis in response to induction with anti-Fas mAb. Thus, the accumulation of activated T cells in IL-2R beta-/- mice does not appear to be derived from abnormalities in either thymic selection or Fas-mediated apoptosis.
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PMID:Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice. 931 Aug 40

Horses with equine infectious anemia virus (EIAV) have episodes of viremia and disease; however, most eventually become inapparent carriers. A possible mechanism of control is cytotoxic T lymphocytes (CTL). To evaluate CTL in inapparent carriers with low viral loads, peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous EIAV-infected PBMC and human IL-2 to detect memory CTL (CTLm). In initial studies, three carriers had CTLm and one of these had low-level effector CTL (CTLe). The CTLm were restricted by equine lymphocyte alloantigen-A (ELA-A) locus encoded MHC class I molecules on autologous equine kidney (EK) target cells. In addition, EK cells did not express MHC class II molecules. The CTLm frequency in PBMC from five inapparent carriers infected for 22 to 50 months was determined by limiting dilution analysis. PBMC were diluted, stimulated, and tested on EK cell targets infected with EIAV and recombinant vaccinia viruses expressing EIAV Env or Gag/Pr proteins. All five carriers had CTLm to EIAV-infected targets, while four had CTLm to targets expressing Env and four had CTLm to targets expressing Gag/Pr proteins. The CTLm frequency range was 60 to 468 per 10(6) PBMC to EIAV-infected targets, 4 to 286 to Env-expressing targets, and 25 to 190 to Gag/Pr-expressing targets. These results should facilitate the identification of epitopes recognized by predominant CTLm from horses controlling a lentivirus infection.
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PMID:Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses. 937 12

Pregnant women, especially primigravidas, are highly susceptible to malaria infection, resulting in maternal anemia and low birth weight infants. Because circulating parasitemia is rare in the newborn, the cause of poor fetal outcomes has been unclear. We measured cytokine concentrations in placentas collected from women delivering in urban hospitals in malaria-holoendemic or nonendemic areas of Kenya. Normal placentas displayed a bias toward type 2 cytokines; type 1 cytokines IFN-gamma and IL-2 were absent in placentas not exposed to malaria but present in a large proportion of placentas from a holoendemic area. TNF-alpha and TGF-beta concentrations were significantly higher, and IL-10 concentrations significantly lower, in placentas from the holoendemic area. Among primigravidas, placental TNF-alpha concentrations were significantly higher in the presence of severe maternal anemia, and both IFN-gamma and TNF-alpha were significantly elevated when a low birth weight, rather than normal weight, infant was delivered. We conclude that maternal malaria decreases IL-10 concentrations and elicits IFN-gamma, IL-2, and TNF-alpha in the placenta, shifting the balance toward type 1 cytokines. This is the first demonstration that these placental cytokine changes are associated with poor pregnancy outcomes in humans.
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PMID:Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. 949 98


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