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)

Colony-stimulating factors (CSFs) are a family of regulatory glycoprotein hormones that promote the proliferation and differentiation of hemopoietic progenitor cells and augment the functions of mature effector cells in vitro. The recent cloning of human genes and the availability of sufficient quantities of recombinant purified growth factors have made it possible to evaluate their therapeutic potential in cytopenic states. Initial studies with GM-CSF have demonstrated its ability to increase neutrophil, monocyte, and eosinophil counts in patients with acquired immune deficiency syndrome (AIDS), myelodysplastic syndrome (MDS), and aplastic anemia. Both GM-CSF and G-CSF reduce the duration of neutropenia following chemotherapy and accelerate hematopoietic recovery in patients undergoing intensive chemotherapy and autologous bone marrow transplantation. Studies are now ongoing to determine the optimal dose, route, schedule of administration, and long-term effects. While the appropriate settings for the use of different CSFs remain to be determined, the initial results of clinical trials are of great interest and suggest that hematopoietic growth factors will play an important role in several clinical arenas.
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PMID:Clinical applications of colony-stimulating factors. 268 11

This study presents the peripheral blood and bone marrow findings in eight children with perinatally acquired HIV infection, ranging in age from 5 months to 3 years. The indications for bone marrow examination were comparable to those for adults with HIV infection and included cytopenia(s), slenomegaly, failure to thrive, and suspected tuberculosis. Thrombocytopenia was the most common indication, and platelet-associated antibodies were elevated in all patients with thrombocytopenia. The peripheral blood morphology was remarkable for the presence of plasmacytosis and eosinophilia in those patients with lymphocytic interstitial pneumonia. Five patients had trephine biopsies, and marrow cellularity was normal with normal or increased megakaryocytes in all cases. Lymphoid aggregates, also described in adult patients with acquired immunodeficiency syndrome (AIDS), were present in three of five trephine biopsies. In contrast to the adult patients, myelodysplasia was not observed in the pediatric age group. None of the eight children had malignancies or opportunistic infections that were diagnosed by bone marrow examination.
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PMID:Hematologic and bone marrow abnormalities in pediatric patients with human immunodeficiency virus (HIV) infection. 274 89

Although immune mechanisms are known to be partially responsible for the thrombocytopenia of patients infected with HIV-1, an understanding of the mechanism underlying this disorder is incomplete. A casual observation that bone marrow biopsies of HIV-infected individuals seem to exhibit an unusually large number of denuded megakaryocyte nuclei (DN-MK) prompted a study comparing MK of 20 HIV-seropositive individuals with those of 10 patients with HIV-negative idiopathic thrombocytopenic purpura and 10 hematologically normal subjects. In normal marrows the number of DN-MK average 2.1 +/- 0.5 SE per 10 low power field. In patients with ITP the average number was 6.5 +/- 1.4 SEM, whereas HIV-ITP marrows had an average of 42.5 +/- 3.7 SEM. Electron microscopy of AIDS megakaryocytes exhibited ballooning of the peripheral zone to an extent not seen by us in any other myelodysplastic syndromes. These observations support the concept that the pathophysiology affecting MK/platelets in HIV-infection should not be equated with the destructive process underlying other immune thrombocytopenias.
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PMID:Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1). 275 19

Research in recombinant DNA technology has led to the characterization of colony-stimulating factors (CSFs) as a family of glycoprotein hormones that are thought to regulate blood cell proliferation and differentiation. CSFs also have been studied for their potential use in treating various hematologic, infectious, and neoplastic disorders. Preliminary-results using granulocyte-macrophage colony-stimulating factor to restore leukocyte competence in acquired immune deficiency syndrome and myelodysplastic syndrome patients have been impressive. Toxic effects generally have not been severe. Other hematopoietic factors are receiving scrutiny for their potential clinical applications.
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PMID:Colony-stimulating factors: present status and future applications. 305 7

Myelodysplastic changes have recently been described in patients with the acquired immunodeficiency syndrome (AIDS). The authors report a patient with AIDS-related complex and myelodysplasia who rapidly progressed to acute myeloblastic leukemia. Infection with human T-cell lymphotropic virus type III (HTLV-III) was documented by culture and by serology. Chromosome studies showed monosomy of chromosome 7 and structural abnormality of the long arm of chromosome 3. The association of HTLV-III infection with myelodysplasia and acute myeloblastic leukemia may have been coincidental in this reported case, but it is also possible that the leukemia was secondary to the HTLV-III infection. Further investigation appears justified.
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PMID:Myelodysplasia progressing to acute myeloblastic leukemia in an HTLV-III virus-positive homosexual man with AIDS-related complex. 346 25

Bone marrow biopsies and smears were examined from 70 patients with acquired immunodeficiency syndrome (AIDS) or AIDS related conditions: 32 patients with AIDS; 9, at risk, group patients with B-cell lymphoma; 22 patients with AIDS related complex (ARC) and 7, at risk, group patients with idiopathic thrombocytopenic purpura (ITP). The first three groups showed similarity with respect to frequency of nonspecific findings: hypo and hypercellularity, marrow damage, lymphoid aggregates, histiocytosis, plasmacytosis and features of myelodysplasia. AFB and fungal organisms were present in the biopsies of 17 per cent of AIDS and 18 per cent of ARC patients. The organisms were associated with bone marrow granulomas or histiocytosis, peripheral lymphopenia and anemia. Only one out of 9 biopsies in patients with previous diagnoses of lymphoma showed involvement of the marrow. One case each of Hodgkin's disease and non-Hodgkin's lymphoma were discovered incidentally among the 22 biopsies from ARC patients without a previous diagnosis of lymphoma. Except for those presenting with ITP alone, bone marrow changes are similar in patients with AIDS and AIDS related conditions.
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PMID:A comparison of bone marrow findings in patients with acquired immunodeficiency syndrome (AIDS) and AIDS related conditions. 349 63

Certain new hematologic findings in eight homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS) are presented. All eight patients manifested a normochromic, normocytic anemia, and six of eight had granulocytopenia during their hospitalization. The other two had low-normal granulocyte counts. Bone marrow examination showed normocellular or hypercellular marrows with increased myeloid: erythroid ratios and increased numbers of megakaryocytes. All patients had abnormalities in maturation of all cell lines, most prominent in the granulocytic series. This constellation of features is similar to the findings in the myelodysplastic syndromes (preleukemia). The authors suggest that myelodysplasia in patients with AIDS results in ineffective hematopoiesis and contributes to the peripheral blood cytopenias found in these patients. Myelodysplasia could be a direct or indirect effect of human T-lymphotropic retrovirus-III (HTLV-III).
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PMID:Myelodysplasia in the acquired immune deficiency syndrome. 402 20

There is general agreement on the fact that bone marrow macrophages present a non-proliferating cell population. Using a sequential double-immunostaining technique, a morphometric analysis was performed on routinely processed bone marrow biopsies derived from 70 patients. The purpose of this study was, firstly, to determine the frequency of bone marrow macrophages in a variety of lesions and, secondly, to elucidate whether there is any proliferative activity detectable by immunohistochemical markers. Bone marrow pathology included reactive myelitis (RM), secondary aplastic anaemia (AP), AIDS-related myelopathy, primary (idiopathic) osteomyelofibrosis (OMF) and myelodysplastic syndromes (MDS). The monoclonal antibody PG-M1 which recognizes a formalin-resistant epitope on macrophages and PC10 raised against proliferating cell nuclear antigen (PCNA) were employed. For comparison with the PCNA-labelling index, the newly developed monoclonal antibody Ki-S1, which is associated with cell proliferation, was applied. In comparison with normal bone marrow, morphometric evaluation revealed a significant increase in macrophages in MDS, OMF, RM and especially in HIV-infected patients. Moreover, a positive immunostaining of single macrophages with PC10 was noted very infrequently. This rather inconspicuous PCNA labelling increased in AIDS. By contrast, Ki-S1 expression was found in none of the other pathologies studied. The prevalence of the macrophage population in certain disorders may have a multifactorial origin, such as inflammatory changes like intercurrent infections in AIDS and enhanced cell turnover in MDS as well as involvement of the complex pathomechanisms generating bone marrow fibrosis. In keeping with previous studies, the insignificant PCNA expression of macrophages should not be related to cell proliferation, but to unscheduled DNA strand repair which may be generated in the course of viral infection in AIDS.
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PMID:Ki-S1 and proliferating cell nuclear antigen expression of bone marrow macrophages. Immunohistochemical and morphometric study including reactive (inflammatory) myelitis, secondary aplastic anemia, AIDS, myelodysplastic syndromes and primary (idiopathic) osteomyelofibrosis. 752 84

The hematopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been cloned, produced in bacteria and yeast, and approved for clinical use in the treatment of neutropenia. Both factors stimulate the proliferation and maturation of neutrophil progenitors and enhance the effector functions of mature cells by interaction with specific receptors on the cell surface. Serum levels of G-CSF correlate inversely with the neutrophil count, suggesting that G-CSF may be the normal homeostatic regulator of the neutrophil count, while GM-CSF is generally undetectable in the serum and appears under normal physiologic conditions to act locally at inflammatory sites. Phase I and II clinical trials with these factors demonstrated minimal toxicity for G-CSF and mild to moderate dose-dependent toxicity for GM-CSF. Recent clinical trials, including double-blind, randomized studies, support a role for these growth factors in the treatment of chronic neutropenias, such as Kostmann's syndrome, acquired immune deficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in acute neutropenias, such as cyclic neutropenia, chemotherapy-induced neutropenia, and bone marrow transplantation.
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PMID:Southwestern Internal Medicine Conference: clinical use of hematopoietic growth factors. 768 52

The colony-stimulating factors (CSFs) have emerged as effective drugs in a variety of clinical situations. These drugs stimulate the production and activity of haematopoietic cells in vitro and in vivo. Two members of this group, granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been approved in the US and Europe for use following cytotoxic chemotherapy and autologous bone marrow transplantation. Other uses of the CSFs include myelodysplastic syndromes, aplastic anaemia, the acquired immunodeficiency syndrome (AIDS) and cyclic and congenital neutropenias. Although CSFs have generally been well tolerated in clinical use there are a number of theoretical concerns, including disease acceleration, biased stem cell commitment and bone marrow exhaustion. New CSFs are currently under development. Combinations of growth factors in the future may maximise effectiveness while minimising toxicity.
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PMID:Use and toxicity of the colony-stimulating factors. 768 34


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