Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 43/4-yr-old black girl with acquired aplastic anemia had an increase in total hemoglobin (Hb) from 4.5 to 16.8 g/dl and fetal hemoglobin (HbF) from 0.8 g/dl (18.8%) to 9.6 g/dl (60.2%) following combined androgen-adrenal steroid therapy. Discontinuation of the drugs was followed by a decline in both HbF and total Hb. Reinstitution of the combined steroids prompted a second rise in total and fetal hemoglobin. During these responses the subject's erythrocytes exhibited an increased i antigen score and a low level of red cell carbonic anhydrase. The glycine:alanine ratio at position 136 of the gamma chains of HbF was of the fetal type (proportion of chains with glycine residues, 0.74). Hemoglobin A2 was low (0.4%). The synthesis of alpha and non-alpha chains was balanced. These results indicate that the stimulation of red cell proliferation in this subject, in response to androgen therapy, resulted in the production of cells with several characteristics of "fetal" erythrocytes.
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PMID:Aplastic anemia with fetallike erythropoiesis following androgen therapy. 63 Jan 18

The hydroquinone and catechol like metabolites, NCQ344 and NCQ436 respectively, of the antipsychotic remoxipride have recently been demonstrated to induce apoptosis in myeloperoxidase (MPO)-rich human bone marrow progenitor and HL-60 cells [S.M. McGuinness, R. Johansson, J. Lundstrom, D. Ross, Induction of apoptosis by remoxipride metabolites in HL-60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia, Chem. Biol. Interact. 121 (1999) 253-265]. In the present study, we determined the molecular mechanisms of apoptosis induced by these remoxipride metabolites in HL-60 cells. Our results show that apoptosis was accompanied by phosphatidylserine (PS) exposure, activation of caspases-9, -3, -7 and DNA cleavage. In HL-60 cells treated with the hydroquinone NCQ344 and catechol NCQ436, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp. fluoromethyl ketone (Z-VAD.FMK) blocked DNA cleavage and activation of caspases-9, -3/-7. In addition, PS exposure was significantly but not completely inhibited by Z-VAD.FMK. These results demonstrate that although Z-VAD.FMK inhibitable caspases are necessary for maximal apoptosis induced by NCQ344 and NCQ436, additional caspase-independent processes may orchestrate changes leading to PS exposure during apoptosis induced by the remoxipride polyphenolic metabolites.
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PMID:Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells. 1099

Severe aplastic anemia (SAA) is a heterogeneous hematological disorder with a high mortality. Genetic predisposition has been shown to play a role in a considerable proportion of SAA cases. For instance, the human lymphocyte antigen HLA-DR2 has been repeatedly demonstrated to be over-represented in SAA patients. In this paper, we expand on the evidence for the contribution of HLA polymorphism in the susceptibility to SAA, which was obtained using the "high-resolution" technique of HLA-DRB1 subtyping. The DRB1*1501 allele appeared to be responsible for the predominance of DR2 specificity in SAA patients and was the most significant risk factor for this disease. It was observed in 23/44 (52.3%) patients versus 22/100 (22.0%) donors [odds ratio (OR) = 3.9; 95% confidence interval (CI): 1.8-8.3; P = 0.0005, corrected P (Pc) < 0.05]. In addition, DRB1*04 alleles also displayed non-random distribution in the SAA group. In particular, DRB1*04 variants coding for alanine at position 74 of the DR beta 1 chain (HLA-DR4-Ala74 beta subtype) were detected in all 13 DR4-positive SAA patients but only in 15/24 (62.5%) controls (OR = 16.6; 95% CI: 0.9-312.0; P = 0.015). Multiple comparison analysis confirmed that the HLA-DR4-Ala74 beta subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74 beta subtype is associated with poor outcome of SAA.
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PMID:HLA-DR4-Ala74 beta is associated with risk and poor outcome of severe aplastic anemia. 1126 26

Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease. Sixty-eight patients (43 males and 25 females) with aplastic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and elevated alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was defined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet count 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for virological and/or serological markers of hepatitis A, B, C, D, E, G viruses, TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 years. The mean interval between onset of hepatitis and first indication of aplastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 patients (59%) achieved complete ALT recovery prior to the diagnosis of aplastic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at the time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 10 of 12 tested cases; two positive results were detected in serum samples obtained after blood transfusion, making the analysis of these positive results difficult. All 17 patients underwent BMT. The mean post-BMT follow-up period was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Relapsing hepatitis was not observed in any of the patients. In conclusion, HAAA is a disease of the young and the etiologic agent associated with HAAA remains unknown. HGV, TTV and parvovirus B19 sequences were not detected in any of the HAAA cases. The survival rate after BMT with stem cells from an HLA-matched sibling is similar to that for patients with non-hepatitis-associated aplastic anemia.
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PMID:Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation. 1128 88