Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present paper, we investigated the pathophysiological implication of TGF-beta from megakaryocytes or megakaryoblasts in the development of myelofibrosis. In the bone marrow of myelofibrosis, proliferation of megakaryocytes is often noticed. We therefore investigated the TGF-beta expression in the bone marrow megakaryocytes from 12 chronic myeloproliferative disorder patients with myelofibrosis by immunohistochemical analysis. About all the specimen showed strong positivity for TGF-beta. In order to examine whether megakaryoblasts produce TGF-beta, we then measured TGF-beta activity in the conditioned medium (CM) of megakaryoblasts from a patient with acute megakaryoblastic leukemia who had profound myelofibrosis. The CM showed strong collagen synthesis stimulating activity which was nullified by addition of anti TGF-beta antibody. Since TGF-beta exists as latent form in platelets, TGF-beta was considered to be altered from active to latent form during megakaryocytes differentiation. In this context, MEG-01, a megakaryoblastic cell line which produces active TGF-beta was underwent differentiation to produce platelet-like bleb with TPA treatment. During the differentiation, MEG-01 showed the decrease of active TGF-beta production and increase of latent TGF-beta together with the production of LTBP. These results suggest that megakaryoblasts produce active TGF-beta and may may cause myelofibrosis, while more differentiated megakaryocytes produce latent TGF-beta. Mechanism by which megakaryoblast escape from negative autocrine of active TGF-beta was also investigated. MEG-01 was found to express mutated p53 which is considered to be responsible for impaired signal transduction of TGF-beta.
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PMID:[TGF-beta and platelet]. 802 82

The integrin family of adhesion receptors includes at least 11 different alpha subunits and 6 different beta subunits which are associated to form 14 different alpha beta heterodimers, divided into three subfamilies. In particular, beta 1 subfamily integrins (VLA 1-6 proteins) have been found to mediate cell adhesion to extracellular matrix (ECM) component such as fibronectin, collagen, laminin; however, VLA-4 has been found to exhibit both cell-cell and cell-matrix adhesion functions. The reactivity of VLAs is virtually ubiquitous and independent of line or tissue specificity. However, the expression of individual VLAs within single tissues can be modulated according to the type or functional status of the cell. One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3. Although the value of VLA3 as an additional marker for the diagnosis of classical B-CLL is indisputable, the biological/functional significance of this reactivity remains to be confirmed.
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PMID:Structure and function of VLA integrins: differential expression in B-cell leukemia/lymphoma. 816 51

In contrast to animal retroviruses such as murine leukemia virus, HIV-1 is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independently of antibody. Evidence is provided for activation of the reconstituted C1 complex by the virus, resulting from direct interaction between C1q and the external part of the viral transmembrane envelope protein (sgp41). Using C1q fragments and synthetic peptides covering the putative interaction regions in C1q and sgp41, we obtain evidence that the C1q/HIV-1 interaction involves: A site on C1q that appears to be located in the intermediary region between the collagen-like and the globular regions of C1q, and which may be conformational, involving two or more C1q chains. A site on gp41 located between residues 601 and 613 (gp160 nomenclature), i.e. within the immunodominant domain of HIV-1. This site shares homology with the corresponding region of HIV-2.
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PMID:Interaction of C1 with HIV-1. 817 63

To analyze the constituents of retroviruses, the Moloney murine leukemia virus was disrupted and observed by dark-field electron microscopy. Virus disruption was achieved by several methods: osmotic shock, freezing-thawing cycles, and exposure to urea up to 4 M, to NaCl up to 1 M, and to Triton X-100. Several components associated with broken Moloney murine leukemia virus were repeatedly found in preparations. These components have been described as rings, thick filaments, chain-like filaments, threads covered with proteins, threads with buckles, and naked threads. A quantitative analysis of the occurrence of these components has been carried out. Among them, the thick filaments composed of a compact helical arrangement of small beads 5 nm in diameter were considered to represent the nucleocapsid. The protease-sensitive buckles found on some threads could be a compact form of the viral RNA associated to the nucleocapsid protein NCp10. The RNase-sensitive naked threads are interpreted as the deproteinized viral RNA itself. The ubiquitous chain-like filaments possess a periodic structure identical to that of polymerized type VI collagen. It is proposed that this adhesive protein is associated with the viral envelope taken from the cell membrane during the budding process of retroviruses.
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PMID:Electron microscopy of the nucleocapsid from disrupted Moloney murine leukemia virus and of associated type VI collagen-like filaments. 825 32

The bone marrow stroma, represented in long-term marrow culture by cells of the adherent layer, is composed of a heterogenous mixture of macrophages and mesenchymal cells, including fibroblasts, endothelial cells and adipocytes, in association with a proteoglycan matrix. This matrix, which is synthesized by the stroma, is capable of binding hematopoietic growth factors, and likely plays a major role in hematopoietic regulation. Clonally-derived non-transformed bone marrow stromal cells, propagated in the presence of basic fibroblast growth factor, were studied for expression of collagenase, an enzyme whose substrate, collagen, is a major component of the extracellular matrix. Expression of steady-state collagenase mRNA was undetectable in both unstimulated dermal fibroblasts and non-transformed marrow stromal cells. However, stimulation with interleukin 1 alpha (10 U/ml) for 24 h resulted in marked accumulation of collagenase mRNA in dermal fibroblast cells, yet failed to elicit a similar response in bone marrow stromal cells. Both marrow stromal cells and dermal fibroblasts constitutively expressed transcripts of collagen I, and rhIL-1 alpha upregulated transcripts of interleukin 6 in both these cells as well. Although similar in morphology, these data indicate that bone marrow stromal cells differ from fibroblasts in their response to IL-1. In the marrow microenvironment, where IL-1 may be secreted by a variety of cell types, such suppression of collagenase expression may serve to prevent unwanted mobilization of collagen from the glycoprotein matrix by marrow stromal cells.
Leukemia 1994 Feb
PMID:Differential expression of collagenase by human fibroblasts and bone marrow stromal cells. 830 54

The susceptibility of rodent hepatocytes to infection by mouse type C retroviruses was examined in vivo and in vitro and compared with the expression of two membrane proteins that function as transporters for the cationic amino acids CAT-1 and CAT-2. CAT-1 expression in rodents determines susceptibility to ecotropic retrovirus infection by serving as the virus receptor. Recently, it has been suggested that CAT-2 may be a receptor for amphotropic murine leukemia virus. In the present study, CAT-1 expression was observed in Hepa1, a cell line derived from a murine hepatoma, and in rat hepatocytes propagated on collagen monolayers in vitro but not in intact or regenerating rat liver in vivo. The expression of CAT-1 correlated with susceptibility to infection by an ecotropic retrovirus encoding beta-galactosidase. CAT-2 expression was observed in hepatocytes in vitro and in vivo, consistent with reports of infection of regenerating and cultured hepatocytes by amphotropic retroviruses. However, introduction of murine CAT-2 into nonpermissive Chinese hamster cells was not sufficient to confer susceptibility to amphotropic retrovirus infection, using a protocol that could easily demonstrate CAT-1-dependent infection by an ecotropic virus. Our data establish CAT-1 as a major determinant of ecotropic retrovirus infection in rodent hepatocytes and suggest that CAT-2 is not a receptor for viruses in the amphotropic subgroup.
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PMID:Retroviral infection and expression of cationic amino acid transporters in rodent hepatocytes. 838 31

Adhesion to bone marrow stroma is a key event in normal B lymphopoiesis, allowing exposure of B-cell progenitors to regulatory cytokines. In order to investigate whether similar processes are important in the proliferation of acute lymphoblastic leukaemia (ALL) cells of precursor-B type, the expression of various adhesion molecules was examined. By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent. CD-44 and VLA-4 were expressed on all 18 cases of precursor-B ALL analysed, while VLA-5 was found on 15 of 18 cases. The integrin CD-11a was detected on 8 of 11 cases, while its ligand, CD-54, was present in 6/12. Other adhesion proteins such as beta 3 integrin, CD-56, CD-15, and Leu8 were not expressed to any significant extent. In view of the known binding of VLA-4 and VLA-5 to extracellular fibronectin (FN), the adhesion of leukaemic cells to FN was evaluated in a colorimetric assay. The precursor-B ALL cell lines REH and KM-3, and 7/15 cases of precursor-B ALL, showed detectable binding to FN. Binding to the other extracellular matrix proteins collagen type 1 and vitronectin was not observed, although two ALL cases showed some binding to laminin. The functional activity of the VLA-4 and VLA-5 molecules was examined using an inhibitory peptide and monoclonal antibodies. These studies indicated that ALL cells adhere to soluble fibronectin predominantly through the VLA-5 molecule (blockable with the PHM-2 antibody and a peptide containing the RGD sequence) although binding mediated by VLA-4 was also apparent in some experiments (blockable by a 40 kDa fragment containing the heparin-binding domain of FN and inhibitory antibodies). These results indicate that precursor-B ALL cells may adhere to marrow stroma through interaction of VLA-4 and VLA-5 with FN, although other mechanisms of adhesion may be important.
Leukemia 1993 Jan
PMID:Adhesion of precursor-B acute lymphoblastic leukaemia cells to bone marrow stromal proteins. 841 84

The clinicopathological features of eight patients with cutaneous disease associated with HTLV-1 infection are reviewed. All were U.K. residents of West Indian extraction, and two are currently alive. Disease remained confined to the skin in two patients. Five patients with a cutaneous prodromal phase developed leukaemia after a median duration of 124 months (3 months-21 years), and in one of these combination chemotherapy produced a sustained clinical remission for 20 months. Two patients developed cutaneous disease after remission of their leukaemia. Cutaneous lesions were heterogeneous and included localized papules, a generalized papulonodular eruption, diffuse and localized erythematous plaques, pompholyx-like lesions on the palms and soles, and tumours. The histology of the skin lesions was also variable, and consisted of a heavy dermal infiltrate with lymphocytes, histiocytes, plasma cells, eosinophils and cytologically atypical mononuclear cells. Epidermotropism was present in biopsies from five patients. Tumour cells with large, densely staining, pleomorphic nuclei, arranged in rows between collagen bundles, were present in the majority of cases. In one patient the infiltrate also consisted of epithelioid cells and multinucleated giant cells. Six cases were classified histologically as pleomorphic T-cell lymphoma, and two as cerebriform or mycosis fungoides type. Molecular studies revealed a clonal T-cell population associated with monoclonal integration of HTLV-1 provirus in tissue DNA from six patients. In two patients HTLV-1 integration was established retrospectively using enzymatic in vitro amplification of a specific HTLV-1 po1 gene sequence in DNA extracted from paraffin-embedded sections. This study indicates that the clinical and pathological features of HTLV-1-associated cutaneous disease are diverse. Patients may have disease confined to the skin for prolonged periods, either at presentation or following clinical relapse--cutaneous adult T-cell lymphoma. Molecular techniques allow distinction from other types of cutaneous T-cell lymphoma, and provide an opportunity for retrospective studies of archival material.
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PMID:HTLV-1-associated cutaneous disease: a clinicopathological and molecular study of patients from the U.K. 850 37

Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon. Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years. We identified 46 other cases by review of the medical literature since 1960. We categorized these 54 cases into three groups according to underlying disease and outcome. Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%). Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness. The survival rate in this group was only 10%. Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy. These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival.
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PMID:Disseminated infection with rapidly growing mycobacteria. 851 48

Factors that predispose to infection in general, of course, may predispose to infection with anaerobes. Included in this category are diabetes mellitus, neutropenia, hypogammaglobulinaemia, malignancy, splenectomy, collagen vascular disease, cytotoxic drug therapy, corticosteroid therapy and other immunosuppression. However, even with these situations there may be certain, more specific, associations: anaerobic cholecystitis and anaerobic osteomyelitis in diabetics, neutropenic colitis, and the increased incidence of local anaerobic infections associated with carcinoma of the lung, colon and uterus. Conditions that lead to decreased redox potential more specifically predispose to infection with anaerobes. Included in this category are obstruction and stasis, tissue anoxia, tissue destruction, vascular insufficiency, prior aerobic infection, burns, foreign body implantation, and calcium salts in a wound (in association with fractures). Other specific clinical situations that predispose to anaerobic infections include leukaemia; oral, gastrointestinal, and female pelvic surgery; trauma at other sites; childbirth; aspiration pneumonia; human and animal bites; and therapy with agents with poor activity against anaerobes (e.g. aminoglycosides, quinolones). AIDS patients appear to be predisposed to severe periodontal disease and its complications.
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PMID:Host factors predisposing to anaerobic infections. 851 53


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