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

1. The nystatin perforated-patch method was used to record macroscopic currents from anti-trinitrophenyl (TNP) immunoglobulin E (IgE)-sensitized rat basophilic leukaemia (RBL-2H3) cells at 37 degrees C. 2. An inwardly rectifying Ca2+ current (ICa) was activated upon stimulation with the multivalent antigen trinitrophenylated bovine serum albumin (TNP-BSA). Induction of ICa was not observed at room temperature. ICa was reversed and reinduced upon cyclical addition of the monovalent hapten dinitrophenyl (DNP)-lysine and multivalent antigen, indicating that a specific interaction of antigen with IgE was required to elicit ICa. 3. The antigen-induced current was also carried by Ba2+ or Sr2+, and to a lesser extent by Na+, in the nominal absence of Ca2+. ICa did not exhibit time-dependent opening (< or = 1 ms) in response to hyperpolarizing voltage steps to -100 mV, although it did accumulate steady-state inactivation of approximately 40-50% over 100 ms. 4. Two inorganic blockers of antigen-stimulated 45Ca2+ influx and secretion, La3+ and Zn2+, inhibited ICa by approximately 50% at concentrations known to produce 50% block of 45Ca2+ influx. In contrast, cromolyn sodium (0.5 mM) and the L-type Ca2+ channel antagonist nitrendipine (5 microM) had no effect on ICa. 5. ICa also was induced by the intracellular Ca2+ mobilizer thapsigargin. Because the actions of thapsigargin and antigen were not additive, IgE receptor cross-linkage appears to activate the recently described capacitative Ca2+ entry channels.
 ...
PMID:Immunoglobulin E receptor-activated calcium conductance in rat mast cells. 777 41

Antibody IgG to human T-cell leukemia virus type I (HTLV-I) in urine was detected by a sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using a synthetic peptide, Cys-env gp46(188-224), as antigen, the sensitivity and specificity of which were 100 and 98.5%, respectively, using serum samples. Anti-HTLV-I IgG in urine was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-Cys-env gp46(188-224) conjugate and Cys-env gp46(188-224)-beta-D-galactosidase (Escherichia coli) conjugate. The complex formed, consisting of the three components, was trapped onto polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. Finally, bound beta-D-galactosidase activity was assayed by fluorometry. Thirty-one urine samples from seropositive subjects and 100 urine samples from seronegative subjects were tested. The sensitivity and specificity were 87 and 100%, respectively, with unconcentrated urine samples and 94 and 100%, respectively, with approximately 10-fold concentrated urine samples. These results were superior to those by the conventional ELISA and gelatin particle agglutination test.
 ...
PMID:Anti-HTLV-I IgG in urine detected by sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using a synthetic peptide, Cys-env gp46(188-224), as antigen. 804 43

Hematologic data from 1,039 persons who participated in the Miyazaki Cohort study on human T-cell lymphotropic virus type-I (HTLV-I) infection were analyzed. Individuals were classified by HTLV-I antibody status and the presence of abnormal lymphocytes (Ably). We identified several differences in selected leukocyte populations: lymphocyte percent was higher among the HTLV-I carriers with Ably (36.5 +/- 2.0%, n = 29) compared with the carriers without Ably (33.1 +/- 0.6%, n = 299) and the seronegatives 36.4 +/- 0.4%, n = 711) (p = 0.04). Conversely, there was a trend of decreasing eosinophil percent among both carrier groups with the lowest percent among carriers with Ably (1.8 +/- 0.5%) compared with the seronegatives (2.8 +/- 0.1%) (p = 0.05). Mean basophil percent was decreased among both carriers groups (p = 0.09). Additionally, red cell count was elevated among the carriers with Ably (461 +/- 7 x 10(4)/mm3) compared with the seronegatives (446 +/- 2 x 10(4)/mm3) (p = 0.03). The HTLV-I carriers with Ably had lower serum albumin (4.39 +/- 0.05 g%) compared with the seronegatives (4.47 +/- 0.01 g%) (p = 0.10). These alterations may be a consequence of HTLV-I infection, with the greatest changes among carriers with Ably, a subset thought to be at risk for developing adult T-cell leukemia.
 ...
PMID:Changes in hematologic parameters among Japanese HTLV-I carriers. 826 58

Several diarylsulfonylureas (DSU), including Sulofenur (LY186641) and LY181984, have been described that exhibit wide spectrum and high therapeutic activity against murine solid tumors and human tumor xenografts. The mechanism for antitumor activity is poorly understood. Moreover, in vitro cytotoxic activity in serum-containing medium is not predictive of in vivo antitumor activity for DSU. Since DSU are extensively bound to serum albumin (> 99%), we sought to determine the effect of albumin on tumor cytotoxicity. We adapted human CCRF-CEM leukemia and GC3 colon carcinoma cells for growth in UltraCHO serum- and albumin-free medium. In comparisons between normal growth medium (RPMI-1640 with 10% fetal bovine serum) and UltraCHO medium, the unbound fraction of drug correlated better with cytotoxic activity than did the total drug. Tumor cytotoxicity by DSU required > 24 h and was markedly enhanced in UltraCHO medium. For example, LY181984 and Sulofenur had IC50 values of 7.4 and 12.1 micrograms/ml against CCRF-CEM in normal growth medium and 0.6 and 0.2 microgram/ml in UltraCHO. Moreover, DSU with the lowest IC-50s in albumin-free medium displayed the most potent in vivo antitumor activity in the 6C3HED lymphosarcoma. A Sulofenur-resistant CCRF-CEM cell line was developed by culturing the cells for > 20 passages in UltraCHO medium containing LY186641 at 2 micrograms/ml (10X IC-50). This line showed approximately 18-fold resistance to LY186641, but did not show cross-resistance to vinblastine, actinomycin D, or doxorubicin. The albumin-free conditions may be useful for further mechanistic studies on the antitumor action by DSU. Further studies are underway to determine whether DSU structural requirements for cytotoxicity an albumin binding are intrinsically linked.
 ...
PMID:Effect of albumin on antitumor activity of diarylsulfonylureas. 829 99

A modified in vitro method to measure murine ovalbumin-specific IgE antibody as an alternative to the in vivo rat passive cutaneous anaphylaxis assay is presented in this report. This assay uses rat basophil leukemia (RBL) 2H3 cells that have been loaded with [3H]serotonin. Exposure of RBL-2H3 cells to mouse antisera and subsequent antigen challenge results in the release of [3H]serotonin. Using a monoclonal mouse anti-DNP IgE antibody and DNP-human serum albumin as the antigen, various steps of this assay were optimized to decrease the amount of time and reagents needed for the assay. The percent [3H]serotonin released was used to calculate antibody titer of sera from ovalbumin-immunized mice. Mouse anti-ovalbumin IgE titers determined by the RBL release method and passive cutaneous anaphylaxis assay were found to correlate very well over a wide range of antibody titers (correlation coefficient, r2 = 0.94).
 ...
PMID:Measurement of murine ovalbumin-specific IgE by a rat basophil leukemia cell serotonin release assay. Comparison to the rat passive cutaneous anaphylaxis assay. 850 56

In 38 patients with acute leukemias or non-Hodgkin's lymphomas of high malignancy the blood-brain barrier (BBB) was prospectively analysed by means of QAlb value (QAlb = cerebrospinal fluid albumin/serum albumin). Cerebro-spinal fluid and serum were taken before each intrathecal methotrexate administration according to central nervous system (CNS) prophylaxis or treatment of CNS involvement by neoplasm. Patients were divided into two groups. Group I consisted of 5 individuals with clinical manifestations of CNS involvement by leukemia or lymphoma. Group II contained 33 patients without neurological symptoms. Besides, group II was subdivided into other two groups: group IIa-patients with BBB analysis before cytostatics application, and group IIb-patients in which BBB was analysed after the administration of at least one cycle of protocols, used in general chemotherapy, including intrathecal methotrexate injection. In group I BBB changes were observed in 10 out of 12 assessments (sensitivity 83.3%). In group II BBB impairment was revealed in 11 out of 52 assessments (specificity 78.8%). The differences in QAlb values between groups I and II were statistically significant (p = 0.0008), whereas there were no significant differences between QAlb values in groups IIa and IIb. Basing on their investigations, the authors conclude that neoplasm invading CNS should be considered as essential risk of BBB impairment, whereas intrathecal and general chemotherapy appear to be less important in BBB injury.
 ...
PMID:[Dysfunction of the blood-brain barrier in patients with acute leukemias or lymphomas of high grade malignancy]. 852 76

Effects of carbachol and antigen (dinitrophenylated bovine serum albumin) on histamine release and histidine decarboxylase (HDC, the enzyme synthesizing histamine) activity were studied in 2H3-m1 cells, a subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors through transfection with the gene. Carbachol stimulated the release of histamine and the activity of HDC with 30-50% the intensity of the maximal effect of the antigen. Pirenzepine, an m1 antagonist, inhibited these carbachol effects in a dose-dependent manner. The effect of the combination of carbachol and antigen on histamine release showed no additivity. These results indicate that these effects of carbachol are exerted via m1 receptors, and they suggest that the actions of carbachol and antigen on histamine release share a common pathway(s), and the release and synthesis of histamine have a positive relationship like in a feedback system.
 ...
PMID:The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors. 856 54

Treatment of rat basophilic leukemia (RBL) 2H3-hm1 cells with Clostridium difficile toxin B (2 ng/ml), which reportedly depolymerizes the actin cytoskeleton, blocked [3H]serotonin release induced by 2,4-dinitrophenyl-bovine serum albumin, carbachol, mastoparan, and reduced ionophore A23187-stimulated degranulation by about 55-60%. In lysates of RBL cells, toxin B 14C-glucosylated two major and one minor protein. By using two-dimensional gel electrophoresis and immunoblotting, RhoA and Cdc42 were identified as protein substrates of toxin B. In contrast to toxin B, Clostridium botulinum transferase C3 that selectively inactivates RhoA by ADP-ribosylation did not inhibit degranulation up to a concentration of 150 microg/ml. Antigen-stimulated tyrosine phosphorylation of a 110-kDa protein was inhibited by toxin B as well as by the phosphatidylinositol 3-kinase inhibitor wortmannin. Depolymerization of the microfilament cytoskeleton of RBL cells by C. botulinum C2 toxin or cytochalasin D resulted in an increased [3H]serotonin release induced by antigen, carbachol, mastoparan, or by calcium ionophore A23187, but without affecting toxin B-induced inhibition of degranulation. The data indicate that toxin B inhibits activation of RBL cells by glucosylation of low molecular mass GTP-binding proteins of the Rho subfamily (most likely Cdc42) by a mechanism not involving the actin cytoskeleton.
 ...
PMID:Inhibition of Fc epsilon-RI-mediated activation of rat basophilic leukemia cells by Clostridium difficile toxin B (monoglucosyltransferase) 863 52

Suramin, a bis-hexasulfonated napthylurea, was studied as an inhibitor of human folylpolyglutamate synthetase (FPGS), a crucial enzyme in folate metabolism. Suramin is a more potent (IC50, 0.9 microM) inhibitor of FPGS partially purified from CCRF-CEM human leukemia cells than is bromosulfophthalein (IC50, 17 microM), the first reported nonsubstrate-analog inhibitor of FPGS (J. J. McGuire et al., Adv. Exptl. Med. Biol. 163, 199, 1983). FPGS inhibition by suramin is reversed by bovine serum albumin (which binds suramin). Suramin is a noncompetitive inhibitor with aminopterin (K(ii) = 0.9 microM; K(is) = 1.1 microM) and glutamic acid (K(ii) = 1.0 microM; K(is) = 5.2 microM) as the variable substrates; suramin inhibition tends toward being competitive with respect to the third FPGS substrate, ATP (K(ii) = 3.4 microM; K(is) = 0.35 microM), since the major effect is on its K(m). Suramin is a much less potent inhibitor of two other folate-dependent enzymes, dihydrofolate reductase (IC50, 38 microM; methotrexate (MTX), 0.6 nM) and thymidylate synthase (IC50, 87 microM; MTX, 48 microM). The effects of suramin on growth of CCRF-CEM cells and a MTX-resistant subline (R30dm) expressing low levels of FPGS activity were determined. R30dm is slightly collaterally sensitive to suramin consistent with FPGS inhibition contributing to the cytotoxic mechanism. These data, and those of Rideout et al. (Int. J. Cancer 61, 840, 1995), demonstrating that the reduced folate carrier system of CCRF-CEM is inhibited, suggest that inhibition of folate metabolism could be involved in the mechanism of action of suramin.
 ...
PMID:Potent inhibition of human folylpolyglutamate synthetase by suramin. 891 44

We have previously shown by reverse transcriptase-PCR (rtPCR) that CML CD34+ HLA-DR- cells are enriched for BCR/ABL(-) hematopoietic progenitor cells (HPC) while leukemic HPC reside predominately within CML CD34+ HLA-DR+ cells. We investigated whether the 30/35 kDa fragment of fibronectin (FN) could be used to enhance retroviral-mediated gene transfer (RMGT) in chronic phase CML marrow HPC. CML CD34+ HLA-DR- and CD34+ HLA-DR+ cells were transduced with vector supernate containing the neomycin resistance gene on plates coated with either FN or bovine serum albumin (BSA) as control, then assayed for transduced HPC in progenitor cell assays in the presence or absence of G418. Transduction efficiency of CML CD34+ HLA-DR- cells over BSA ranged from 0.09 to 7.2% (mean 3.3 +/- 1.5%), while that over FN plates ranged from 3.8 to 23% (mean 11.0 +/- 4.5%) (n = 4). Transduction efficiencies of CML CD34+ HLA-DR+ cells ranged from 0.4 to 9.8% (mean 3.7 +/- 1.7%) and 6.0 to 26% (mean 17.3 +/- 4.5%) (n = 5) over BSA and FN, respectively. rtPCR analysis for BCR/ABL mRNA of individual G418-resistant HPC generated from CD34+ HLA-DR- cells revealed that normal BCR/ABL(-) HPC were successfully transduced under these experimental conditions. These results demonstrate the feasibility of transducing normal CML primitive HPC, and illustrate the potential clinical use of FN in the setting of gene therapy for CML, as well as other diseases.
Leukemia 1997 Jan
PMID:The 30/35 kDa chymotryptic fragment of fibronectin enhances retroviral-mediated gene transfer in purified chronic myelogenous leukemia bone marrow progenitors. 900 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>