UMLS:C0023418 - FACTA Search

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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to separate graft-versus-leukemia (GVL) effect from graft-versus-host (GVH) reactions in allogeneic cell therapy, we established cytotoxic T cell lines (CTL) against irradiated A20, WEHI-3 and PU cells, ie cells from 3 hematopoietic tumors of Balb/c origin. Immunization with these cell lines did not lead to prolonged survival in Balb/c mice. The cytotoxic activity of the CTL was tested against the 3 leukemias. In all 9 combinations the highest specific lysis was achieved against the stimulating tumor. Cold target inhibition experiments showed that the activity against 51Cr-labelled leukemia cells could be almost completely inhibited by adding a sufficient amount of unlabelled target cells. On the other hand, when unlabelled concanavalin A-induced Balb/c blast cells were added, the inhibition was incomplete. By means of flow cytometry it was excluded that the different susceptibilities and inhibitory potentials of tumor cells and nonmalignant blasts are caused solely by differences in the MHC expression of the target cells. These findings confirm that allogeneic CTL are capable of discriminating malignant from nonmalignant cells, even if the tumor is nonimmunogenic in syngeneic animals.
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PMID:Allogeneic mouse T cell lines distinguish three Balb/c leukemias from each other and from non-leukemic lymphocytes. 853 18

We have adapted and developed a PCR (polymerase chain reaction)-based technique for the T-cell receptor (TCR)-gamma chain gene, which has subsequently been used for routine diagnosis. Variable-region oligonucleotide primers were chosen from subgroups I and II, and the joining region primer was from the J2 segment. The primers were used to perform a 32P-incorporation PCR, and the products were then separated on an 8% denaturing polyacrylamide gel. In our hands, this technique is more reliable than cold methods, when separation is performed on either agarose or nondenaturing polyacrylamide. The radioactive technique was used to look at 102 T-cell proliferations, of which eight of eight T-acute lymphoblastic leukemia (ALL), 24 of 34 T-non-Hodgkin's leukemia (NHL), and 35 of 60 large granular lymphocyte (LGL) expansions were clonal. Of 122 B-cell proliferations investigated, including 72 cases of B-cell lineage ALL, 36 demonstrated a T-cell rearrangement (33 ALLs and three myelomas). Samples from nonlymphoid tumors were tested and produced a normal distribution ladder of PCR products after autoradiography, a pattern also observed with antenatal and preoperative patients. The radiolabel-incorporation method detected an abnormal pattern of a ladder with prominent dark bands in 29 of 122 B-cell and 27 of 102 T-cell cases and in 0 of 49 of the nonlymphoid and normal samples. The abnormal banding patterns obtained in a proportion of the B- and T-cell cases was not readily discernible by nondenaturing-acrylamide or agarose-separation methods.
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PMID:32P-incorporation PCR for the detection of rearrangements at the TCR-gamma locus. 895 23

Hairy-cell leukaemia may be difficult to diagnose in bone marrow biopsies, especially in the early stages or in its residum after complete clinical remission. To consider the impact of published data on immunophenotyping hairy-cell leukaemias, a total of 50 diagnostic biopsies were systematically analysed with a panel of eight antibodies and compared with cases of chronic lymphatic leukaemia (CLL), 20 follicular centre lymphomas, 20 lympho-plasmacytoid immunocytomas, 10 small-cell T-cell non-Hodgkin lymphomas and 20 cases of benign nodular lymphatic hyperplasia. The panel of eight antibodies comprised DBA44, CD45, CD20, CD45R, CD45RO, CD43 and the CD68 antibodies KP1 and Ki-M1P. The hairy-cell leukaemias were staged histologically into four categories of bone marrow infiltration. DBA44 reacted positively in 47/50 cases. CD45 and the B-cell markers CD20 and CD45R reacted in 49/50 and 43/50 cases, respectively. One CD68 marker, KP1, was positive in 38/50 cases but the other-Ki-M1P-only in 1/50 cases. Chronic lymphatic leukaemia cases, the other B-cell NHLs and lymphatic hyperplasias showed strong positivity for CD20 and CD45R, but only the immunocytomas reacted with DBA44 in 7/20 cases. The T-cell NHLs and hyperplasias showed a strong positivity for the T-cell markers CD45RO and CD43. The CD68-marker Ki-M1P revealed a high specificity since it was negative in all NHLs and positive only in one hairy-cell leukaemia. Methyl-methacrylate embedding of bone marrow biopsies under cold polymerization produces a high quality of histo- and cytomorphology, resulting in greater diagnostic reliability and the detection of low-stage infiltration of hairy-cell leukaemia. DBA44 appears as a highly specific antibody to mark hairy-cells since only immunocytomas reacted positively in a few cases. A small panel of antibodies including DBA44. CD20, CD45R and Ki-M1P may serve to distinguish small-cell. NHL from hairy-cell leukaemia even at an early stage or when there are minimal residual tumour cells.
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PMID:Immunophenotype of hairy-cell leukaemia after cold polymerization of methyl-methacrylate embeddings from 50 diagnostic bone marrow biopsies. 906 39

Commenting on a case report of dermal immunocytoma with crystal-storing histiocytes, a short review is given on the phenomena related to crystallization of monoclonal immunoglobulins within plasma cells, in the extracellular space, or within the lysosomal compartment of macrophages. Paraprotein crystallization is supported by hydrophobicity, poor solubility in the cold or at acid pH, and there are few reports on structural defects of crystal-forming myeloma proteins which are supposed to promote either their crystallization or impaired intralysosomal degradation. In the hitherto known cases of crystal histiocytosis, immunoglobulins of light chain type kappa have been exclusively involved in the process of macrophage storage. Accumulation of paraprotein-related crystals in macrophages may mimic the appearance of Gaucher cells or of the so-called pseudo-Gaucher cells seen in chronic myelogeneous leukaemia. With regard to their lightmicroscopical and ultrastructural differences to both, Gaucher cells and pseudo-Gaucher cells, paraproteinaemia-related crystal-storing macrophages may be denoted as pseudo-pseudo-Gaucher cells (PPGC). Human PPGC are similar to constitutive crystal-storing histiocytes known from inbred C57 BL-6 mice. The distribution of PPGC may be limited to the realm of a plasmacytoma or immunocytoma, but there are also cases with systemic involvement of the RES similar to Gaucher disease.
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PMID:Gammopathy-related crystal-storing histiocytosis, pseudo- and pseudo-pseudo-Gaucher cells. Critical commentary and mini-review. 912 35

It has previously been shown that human granulocyte-macrophage colony-stimulating factor (GM-CSF) can be fused to a truncated diphtheria toxin (DT) to produce a recombinant fusion toxin that kills GM-CSF receptor-bearing cells. We now report that DT388-GM-CSF induces apoptosis and inhibition of colony formation in semisolid medium in receptor positive cells, and that the induction of apoptosis correlates with GM-CSF-receptor occupancy at low ligand concentrations. Also, the induction of apoptosis correlates with the inhibition of protein synthesis and is inversely related to the amount of intracellular antiapoptotic proteins (Bcl2 and Bc1XL). Nine myeloid leukemia cells lines and four nonmyeloid leukemia cell lines were incubated with 0.7 nmol/L of 125I-GM-CSF in the presence or absence of excess cold GM-CSF and bound label measured. High affinity receptor numbers varied from 0 to 291 molecules per cell. Cells were incubated with varying concentrations of recombinant fusion toxin for 48 hours and incorporation of 3H-leucine (protein synthesis), segmentation of nuclei after DAPI staining (apoptosis), and colony formation in 0.2% agarose (clonogenicity) were measured. DT388-GM-CSF at 4 x 10(-9) mol/L inhibited colony formation 1.5 to 3.0 logs for receptor positive cell lines. Protein synthesis and apoptosis IC50s varied among cell lines from greater than 4 x 10(-9) mol/L to 3 x 10(-13) mol/L. GM-CSF-receptor occupancy at 0.7 nmol/L GM-CSF-ligand concentration correlated with the protein synthesis IC50. Similarly, the protein synthesis inhibition and apoptosis induction correlated well, except in cells overexpressing Bcl2 and BclXL, in which 25- to 150-fold inhibition of apoptosis was observed. We conclude that DT388-GM-CSF can kill acute myeloid leukemia blasts but that apoptotic sensitivities will depend on the presence of at least 100 high affinity GM-CSF receptors/cell and the absence of overexpressed antiapoptotic proteins.
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PMID:Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein. 934 50

The XIX Symposium of the International Association for Comparative Research on Leukemia and Related Diseases (IACRLRD, President: Prof. Dr. R. Hehlmann) was held in Mannheim and Heidelberg, Germany, July 13 - 18, 1997. Comparative research in cancer was systematically established in the 1950s. Similarities in morphology, biology and pathology between animal and human leukemias and related diseases and the viral origin of a variety of animal leukemias and related diseases (lymphomas, sarcomas, breast tumors etc.) led to the concept that comparative research should promote the understanding of human leukemias and related diseases. In 1960 the World Health Organization inaugurated the establishment of a World Committee for Comparative Leukemia Research. The first symposium took place in Hannover, Germany, in 1963. After the fifth symposium in Padova, Italy, in 1971 the International Association for Comparative Research on Leukemia and Related Diseases (IACRLRD) was founded to complement the World Committee and to expand the international effort. The history of the symposium shows the evolution from a meeting on animal leukemia viruses into one dealing with viral and genetic aspects of human and animal leukemia and related diseases. The scientific evolution of the Abelson murine leukemia virus with its abl oncogene in the 1970s to what currently appears as the most reliable marker for human chronic myeloid leukemia is merely one example. Comparative research has reached a new dimension with the the recent advances in sequencing of the genomes of a variety of species and of humans. Many genes identified in the human genome and relevant for disease can be found in the genomes of animal species and even in the genomes of bacteria and of yeast. This reminds us that not just human and animal biology but also pathology must be regarded as a continuum of evolution and that much can be learned from comparing the genetic information of different species. Comparative genome research will allow conclusions to be drawn from principles recognized in animal species which are relevant to human diseases. It is likely that the application of comparative research to genome analysis will provide basic new insights in molecular medicine into the function of living beings for both animal species and humans. The current revolution in genomics is the latest phase in a rich history of medical progress related to the comparative approach. Meetings and organizations that have grown out of IACRLRD, include, at least to some extent: the Meeting of the International Human Retrovirology Association, the Gallo Lab Meeting , the Feline Retrovirus Meeting, the Cold Spring Habor Retrovirus Meeting, international and regional AIDS meetings, and many others. The XIX symposium in Mannheim included five memorial lectures, seven plenary sessions, 18 parallel sessions, two round table discussions and a public forum. In addition, six associated satellite symposia were held. The general meeting, attended by participants from 27 countries, integrated thematically contributions of genetic, cellular, and viral factors toward the development of leukemia and lymphoma and sought unifying concepts in leukemogenesis.
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PMID:Congress Report: XIX symposium of the International Association for Comparative Research on Leukemia and Related Diseases, Mannheim/Heidelberg, Germany, July 13 - 18, 1997. 953 31

TCRalphabeta CTL clones recognizing mouse thymus leukemia (TL) Ags were established and categorized into two groups: those killing any TL+ target cells (type I) and those killing only TL+ Con A blasts (type II). Cold target inhibition assays showed that the antigenic determinant(s) recognized by type II clones are expressed not only on TL+ Con A blasts but also on other TL+ target cells. The relation of the target specificity to the killing machinery and the accessory molecules involved in cytotoxicity were therefore analyzed using four representative clones selected from each type. Of the target cells tested, Fas was only expressed on Con A blasts, indicating that Fas ligand (FasL)-dependent cytotoxicity is limited to such cells. All four type II and one of four type I clones expressed FasL on the surface, while both types contained perforin in the cytoplasm. Blocking studies using neutralizing anti-FasL mAbs and concanamycin A (CMA), a selective inhibitor of the perforin pathway, suggested that type I clones kill target cells by way of perforin, while type II clones kill TL+ Con A blasts through FasL together with perforin. For their cytotoxicity, type I CTLs require a signal through CD8, while type II require LFA-1/ICAM-1 interactions. Type II clones also need a co-stimulatory signal through an unknown molecule for perforin-dependent cytotoxicity. These results taken together suggest that the difference in the target specificity of anti-TL CTL clones is due to variation in the killing machineries and the dependence on accessory molecules.
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PMID:Two types of anti-TL (thymus leukemia) CTL clones with distinct target specificities: differences in cytotoxic mechanisms and accessory molecule requirements. 960 21

Following bone marrow stem cell transplantation allo-responses against haemopoietic progenitor cells (HPC), causing graft rejection and graft-versus-leukaemia effects, can be induced by donor T cells recognizing peptides derived from polymorphic endogenous proteins present in HPC. Since CD33 and CD34 are both expressed on HPC, we looked for genetic polymorphisms that might be the source of minor histocompatibility antigens (mHA) on such cells. Bone marrow from 14 donors and their HLA-identical recipients undergoing BMT for haematological malignancies were studied. Using non-radioactive single-strand conformation polymorphism analysis (cold SSCP) of complementary DNA encoding CD33 and CD34, three DNA polymorphisms, two in CD33 and one in CD34 were found and sequenced. Two were in non-coding regions, but in CD33, ATA or ATG at codon 183 resulted in an Ile or Met in the protein sequence. Nonapeptides derived from both alleles were predicted to bind to HLA A68.1. Thus two alleles of CD33 protein exist that could be mHA. With an alternate allele frequency of < 10%, allo-responses against CD33 would be uncommon after marrow transplantation. However, donors homozygous for this allele could be used to generate cytotoxic T cells against the frequent CD33 allele, for adoptive therapy of leukaemia.
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PMID:Polymorphism in CD33 and CD34 genes: a source of minor histocompatibility antigens on haemopoietic progenitor cells? 975 70

In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.
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PMID:Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration. 1007 88

Investigate mutation of ras gene family in various stage of gastric cancer in China. PCR-RFLP, PCR-SSCP and PCR-DNA sequencing were used to detect mutation rates of H-ras, K-ras and N-ras gene. Mutation rates of H-ras at 12 codon in metaplasia, atypical hyperplasia, and progressive gastric cancer is 16.7% (6/36), 31.2% (15/48), 34.7% (25/72), respectively. In groups of superficial gastritis and normal control, no mutation were found. Mutations of H-ras 61 codon and N-ras 12 codon in various groups were the same as normal. Only 2 cases of K-ras 12 codon mutation were detected in gastric cancer by PCR-SSCP, but it was not identified by DNA sequencing. It may be of polymorphism. All H-ras 12 codon mutation were G-->T mutation. There are significant difference between groups of metaplasia, dysplasia, and gastric carcinoma comparing with group of normal control (P < 0.05, P < 0.01, P < 0.01). H-ras 12 codon mutation maybe an early event and maybe play important role in gastric carcinogenesis. Although K-ras mutation rate is high in colon cancer and leukemia it seemed to be relationship with gastric cancer. High frequency of H-ras 12 codon mutation maybe the characteristic of gastric cancer and associate with high incidence of gastric cancer in China. Three methods used in this experiment were compared that SSCP method is more sensitive than RFLP and cold SSCP is simpler and likely to be used in clinic.
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PMID:[Detection of ras gene mutation in various stages of gastric cancer by PCR/RFLP SSCP and DNA sequencing]. 1043 68

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