Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report instances of fatal leukoencephalopathy associated with the intravenous administration of the antifungal agent amphotericin B (AmB) to a 16-year-old girl treated for acute lymphoblastic leukemia and a 22-year-old man who underwent bone marrow transplantation for a myelodysplastic syndrome. Both received AmB in association with cranial irradiation and developed a subacutely evolving neurologic disorder characterized by personality change and confusion rapidly progressing to akinetic mutism. Neuroimaging studies disclosed diffuse nonenhancing abnormalities of the cerebral, particularly frontal, white matter that included hypodensity on CT and increased signal on T2-weighted MRI. Postmortem examinations demonstrated a diffuse, noninflammatory leukoencephalopathy with florid astrogliosis, demyelination, and infiltration of the hemispheric white matter by foamy macrophages. In neither case was there evidence of opportunistic infection or neoplastic infiltration of the nervous system. We review the evidence that polyene macrolide antibiotics such as AmB are potential leukotoxins.
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PMID:Amphotericin B-associated leukoencephalopathy. 140 84

Bone marrow biopsies from 125 patients at different stages of HIV infection were examined and the histopathological changes are described. Indications for biopsy included peripheral blood abnormalities, search for opportunistic pathogens, a suspected lymphoma or evaluation of its progression. Common histopathological features, suggestive of HIV infection but non-pathognomonic, were: severe hypercellularity (43.2%), myelodysplasia (74.4%), plasmocytosis (86.4%), and lymphocytic (36.8%) and histiocytic infiltrates with or without granulomas (20%). Reticular fibrosis (58.6%), iron deposits (59.2%), vascular congestion and mucoid degeneration of fat (18.4%) were frequently observed. Hypoplasia was usually a late-occurring event and/or may have been iatrogenic. Opportunistic infections were detected in 8 patients: Mycobacterium avium intracellulare (4 cases), Mycobacterium tuberculosis (1 case), Cryptococcus neoformans (1 case), and Leishmania (1 case). Neoplastic complications were found in 3 patients: Burkitt's lymphoma (1 case) and Hodgkin's disease (2 cases). The pathophysiological mechanisms envisaged include the effect of HIV infection on precursor cells in the bone marrow.
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PMID:[The bone marrow in human HIV infection. A bioptic study of 125 cases]. 152 53

The histopathologic changes of bone marrow during infection with the human immunodeficiency virus type 1 (HIV-1) are described. Bone marrow biopsies from 73 patients at different stages of HIV-1 infection were studied. Indications for biopsy included peripheral blood abnormalities, suspicion of lymphoma, or search for specific pathogens. Common histopathological features, suggestive of HIV-1 infection but nonpathognomonic were hypercellularity (67%), myelodysplasia (86.1%), plasmacytosis (98.6%), lymphocytic infiltration (31.1%) and histiocytic infiltration with or without granulomata (13.7%). Increases in reticulin fibers (54.7%), and stainable iron deposits, vascular congestion and serous atrophy of fat were frequent features. Opportunistic infections and neoplastic complications were detected in 7 cases: pathogens were demonstrated in 4 cases (Mycobacterium avium intracellulare (MAI), Cryptococcus neoformans, Toxoplasma gondii and Leishmania) and lymphoma in 3 cases (1 Burkitt lymphoma and 2 Hodgkin's disease). Bone marrow hypoplasia is usually a terminal event in AIDS and may be iatrogenic.
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PMID:Bone marrow findings in HIV infection: a pathological study. 210 65

The relative benefit of allogeneic bone marrow transplantation (alloBMT) vs autologous BMT (autoBMT) for patients with relapsed or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) remains uncertain. Toxicity from graft-versus-host disease (GVHD) may diminish the potential benefits both of graft-versus-tumor activity and of receiving uncontaminated donor marrow stem cells. From 1987 to 1995, 27 adults (ages 18-60 years; median 36) underwent alloBMT for lymphoma after failure of standard chemotherapy. Twenty-one had NHL and six had HD (nodular sclerosis). Thirteen patients had primary refractory disease or chemotherapy-resistant relapses; two of these had relapsed after autoBMT. Three patients had untested relapses (one of them had relapsed after autoBMT), and 11 had chemotherapy-sensitive relapses. Twenty-four received HLA-matched bone marrow from a sibling (one twin); three received haploidentical marrow cells. Nine (33%) died from lymphoma. Eleven (41%) died of treatment-related causes. Opportunistic infections were a substantial problem leading to eight of these deaths (30%). Six patients (22%) survive free of lymphoma 17-70 months post-BMT (median, 56 months); four had had sensitive relapses, one had had a resistant relapse, and one had had nontested relapse. Three have chronic GVHD (limited in one; extensive in two). One HD patient who had relapsed after autoBMT remains in remission 19 months after alloBMT. No therapy-related myelodysplasia has been observed. We conclude that alloBMT has substantial morbidity in heavily pretreated lymphoma patients due to acute toxicity, infections and GVHD. However, 22% of our HD/NHL patients have had long-term disease-free survival.
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PMID:Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma. 933 51

Polymorphonuclear leukocytes are essential for host defense to infectious diseases. CCAAT/enhancer binding protein epsilon (C/EBP epsilon) is preferentially expressed in granulocytes and lymphoid cells. Mice with a null mutation in C/EBP epsilon develop normally and are fertile but fail to generate functional neutrophils and eosinophils. Opportunistic infections and tissue destruction lead to death by 3-5 months of age. Furthermore, end-stage mice develop myelodysplasia, characterized by proliferation of atypical granulocytes that efface the bone marrow and result in severe tissue destruction. Thus, C/EBP epsilon is essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells.
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PMID:Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice. 937 21

Immunological abnormalities (IA) are frequently observed in patients with myelodysplastic syndromes (MDS). Although there have been a number of analyses of the prognostic factors, there have been few studies, if any, to determine whether IA affects prognosis. We investigated the prognosis of 153 MDS patients with or without IA who were treated at a single Japanese institute for 10 years. Nineteen of 153 patients (12%) developed autoimmune disorders. One hundred of 153 patients (63%) had an abnormality in at least one immunological laboratory test. Hypergammaglobulinemia was found in 50 of 128 (39%) patients tested, hypogammaglobulinemia was observed in 10 of 128 (8%), positivities of antinuclear antibody, RA factor. DNA antibody, and direct antiglobulin test were observed in 30%, 14%, 7% and 12%, respectively, and a CD4/CD8 ratio < 1 was observed in 20%. There was no significance in the distribution of age, MDS subtype, or sex between patients with and without IA. The survival of MDS patients without IA was significantly better than that of patients with IA, and the survival of patients with a CD4/CD8 ratio > 1 was also significantly superior to the survival of those with an inverted CD4/CD8 ratio. Patients with IA tended to die of infection or leukemic progression in comparison with those without IA, suggesting that IA may be associated with susceptibility to opportunistic infection and disease progression.
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PMID:Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients. 2733 45

We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression.
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PMID:Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation. 1137 48

The Pur protein family consists of four known members in humans, the prototype gene for which is strongly conserved throughout evolution. Several investigations have now implicated Pur alpha in pathways of inhibition of oncogenic transformation. Clues to the potential importance of Pur family members in cancer are derived from observations of genetic alterations of both Pur alpha and Pur beta in myelodysplastic syndrome progressing to acute myelogenous leukemia. A role for newly-discovered Pur gamma in neoplasia is also beginning to emerge as studies have indicated that cellular levels of two Pur gamma isoforms are elevated in certain tumors. A variety of studies have now implicated Pur alpha in development of blood cells and cells of the central nervous system. Clues to the functions of Pur alpha, a key family member, have recently been derived from studies of the interactions of HIV-1 and JC virus (JCV) in AIDS. JCV causes an opportunistic infection in the brains of certain HIV-1-infected individuals. Pur alpha can influence this viral interaction through functional associations with the Tat protein and TAR RNA of HIV-1, and with large T-antigen and DNA regulatory regions of JCV. Evidence is now strong that Pur alpha interacts with both DNA and RNA and that an important aspect of its function is to recruit regulatory proteins to specific nucleic acid sequences in processes as diverse as DNA replication, gene transcription, RNA transport in the cytoplasm and compartmentalized mRNA translation.
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PMID:The Pur protein family: clues to function from recent studies on cancer and AIDS. 1289 83

Accelerated programmed cell death or apoptosis appears to play an important role in the pathogenesis of myelodysplasia. As overexpression of TNF-alpha has been described to induce cell death in myelodysplasia, treatment with anti-TNF-alpha is currently being explored. Caution is needed because of an increased risk of opportunistic infection during anti-TNF-alpha treatment. We here describe a patient who was treated with anti-TNF-alpha for low risk myelodysplasia and died of invasive mucormycosis.
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PMID:Mucormycosis in a patient with low risk myelodysplasia treated with anti-TNF-alpha. 1719 57

What is believed to be the first clinical isolate of Bordetella hinzii in the UK, from a patient with myelodysplastic syndrome, is described. This patient had no known avian exposure, and the source of the organism remains unknown. It appears that the underlying immune deficiency of the patient increased the susceptibility to opportunistic infection with this organism. Human infection with B. hinzii is rare and this species is difficult to differentiate from Bordetella avium by routine phenotypic methods. Confirmation can be reliably achieved using genotypic methods, and the greater mutational variation of the ompA gene compared to other genes (e.g. 16S rRNA gene) allows unambiguous identification of this and other non-classical Bordetella species.
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PMID:A UK clinical isolate of Bordetella hinzii from a patient with myelodysplastic syndrome. 1803 44


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