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)

Rat basophilic leukemia cells were labeled either enzymically with 125I or biosynthetically by culture in the presence of 14C-glucosamine or 3H-amino-acids and then extracted with NP-40. IgE-anti-IgE precipitates insolubilized a radiolabeled macromolecule from these extracts largely or entirely absent in control IgG-anti-IgG percipitates. When specific precipitates were boiled in sodium dodecyl sulfate (SDS) and analyzed by polyacrylamide gel electrophoresis in the presence of SDS, most of the 14C or 125I radioactivity was in the area corresponding to an apparent m.w of 60,000 to 70,000 in 5.9% gels. In 10% and 12% gels, faster mobility was demonstrated indicating an atypical electrophoretic behavior often associated with glycoproteins and a presumptive m.w. of 50,000 or less. Since only IgE-containing precipitates localized label in this region and since such precipitates from cells saturated with IgE prior to surface iodination failed to show this band, the labeled macromolecule appears to be the IgE receptor itself. Analysis of the acid hydrolysates of precipitated 14C radioactivity demonstrated that label was entirely in hexosamines and sialic acid. 125I and 14C labels in the recepotr region were eliminated almost completely with pepsin and pronase and to a lesser extent with trypsin.
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PMID:The rat basophilic leukemia cell receptor for IgE. I. Characterization as a glycoprotein. 82 Aug 4

Retroviruses encode proteinases necessary for the proteolytic processing of the viral gag and gag-pol precursor proteins. These enzymes have been shown to be structurally and functionally related to aspartyl proteinases such as pepsin and renin. Cerulenin is a naturally occurring antibiotic, commonly used as an inhibitor of fatty acid synthesis. Cerulenin has been observed to inhibit production of Rous sarcoma virus and murine leukaemia virus by infected cells, possibly by interfering with proteolytic processing of viral precursor proteins. We show here that cerulenin inhibits the action of the HIV-1 proteinase in vitro, using 3 substrates: a synthetic heptapeptide (SQNYPIV) which corresponds to the sequence at the HIV-1 gag p17/p24 junction, a bacterially expressed gag precursor, and purified 66 kDa reverse transcriptase. Inhibition of cleavage by HIV-1 proteinase required preincubation with cerulenin. Cerulenin also inactivates endothiapepsin, a well-characterised fungal aspartyl proteinase, suggesting that the action of cerulenin is a function of the common active site structure of the retroviral and aspartic proteinases. Molecular modelling suggests that cerulenin possesses several of the necessary structural features of an inhibitor of aspartyl proteinases and retroviral proteinases. Although cerulenin itself is cytotoxic and inappropriate for clinical use, it may provide leads for the rational design of inhibitors of the HIV proteinase which could have application in the chemotherapy of AIDS.
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PMID:In vitro inhibition of HIV-1 proteinase by cerulenin. 169 Jan 52

The avian sarcoma/leukemia virus protease (PR), purified from avian myeloblastosis virus has a native molecular mass of 26 kDa, suggesting a dimer structure. The enzymatic activity of PR has been characterized using synthetic peptide substrates. PR is most active at pH 5.5, 35 degrees C and 2-3 M NaCl. Under these conditions PR cleaves decapeptides which are resistant in low ionic strength. This high, nonphysiological, salt concentration also increases the proteolytic activity of a cellular aspartic protease, pepsin. PR and pepsin show additional similarities: they both cleave a synthetic decapeptide at the same Tyr-Pro bond in low and high salt, while the cleavage site preferences of human renin and cathepsin-D in this substrate are altered at high salt concentrations. In addition, iodination of the tyrosine residue in this decapeptide causes an increase in the rates of hydrolysis by both PR and pepsin. However, Km values are too high to be estimated accurately for PR using Tyr-Pro and Tyr(I)-Pro decapeptides as substrates. Comparison of the digestion products of two additional decapeptides, altered in a single amino acid residue, shows that PR cleaves at fewer sites than all three cellular enzymes. Furthermore pepstatin, a strong inhibitor of pepsin, renin, and cathepsin-D has little effect on PR.
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PMID:Avian retroviral protease and cellular aspartic proteases are distinguished by activities on peptide substrates. 253 48

A 48-yr-old man with chronic myelogenous leukemia and basophilia developed a duodenal ulcer and hemorrhage. Gastric analysis revealed basal hyper-secretion of acid (33.1 mEq/h) and pepsin (44.5 x 10(-4) peptic units/h). Blood, serum, and urine histamine was elevated and serum gastrin was normal. Although acid output was markedly suppressed with ranitidine (50 mg i.v.), pepsin secretion was only inhibited 63% and had returned to basal levels by the sixth hour. Maximal acid output does not suggest a trophic effect of histamine in this patient. The previously reported cases of basophilic leukemia and gastric hypersecretion or duodenal ulcer disease are reviewed.
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PMID:Basophilic leukemia and the hypersecretion of gastric acid and pepsin. 313 Nov 79

Rat leukemia cells IRC 741 in suspension culture form single cytoplasmic protrusions by which the cells preferentially adhere to one another. The induction and/or maintenance of these protrusions is sensitive to changes in intercellular contact, pH, temperature, and nutritional conditions. The protrusions are stable, rigid structures which take part in intercellular adhesion but not in adhesion to substrata. Movement on substrata occurs by means of ruffling membranes formed on the main cell body. This asymmetry in cellular form and function is associated with specialized cell surface regions. Ultrastructurally, the cell surface over the protrusions lacks microvilli, and is covered with a 3,000-4,000-A thick cell coat consisting of 200-500-A electron-dense particles in an amorphous matrix. In contrast, the surface over the main cell body has microvilli and a 200-A wide cell coat which lacks particles. The extracellular particles overlying the protrusions have electron-lucent cores, are protease- and pepsin-resistant, and do not stain with colloidal iron, while the matrix in which they are embedded is sensitive to proteolytic enzymes and contains acidic moieties. The negative surface charge density over the protrusions is higher than that over the main cell body, as shown by the orientation of the cells in an electric field. The unexpected observation that a region of higher charge density is one of increased intercellular adhesiveness might be explained, in part, by the rigidity of the protrusions and by the very small radius of curvature of the overlying extracellular particles. The protrusions permit the observation of discrete regions, differing in charge density, on the surface of living leukemia cells.
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PMID:Structural and functional heterogeneity of the surface of rat leukemia cells. 427 52

Specific viral transformation rather than cell selection can explain the previously observed increase in the proportion of type III procollagen compared to type I procollagen in BALB 3T3 cells transformed by Kirsten murine sarcoma virus (Ki-MSV). Two subclones of BALB 3T3 A31 were productively infected with with a temperature-sensitive Ki-MSV in the presence of helper murine leukemia virus (MLV), resulting in virtually complete transformation of cultures and eliminating selection of transformed foci. Analysis of radioactive collagen, derived from procollagen by pepsin treatment, showed that both of the tsKi-MSV/MLV-transformed subclones contained a 4-fold greater proportion of type III procollagen than did control MLV-infected cultures. A nonproducer derivative exhibited an even greater change (10-fold), indicating that viral replication was irrelevant. After 48 hr at a nonpermissive temperature, tsKi-MSV-transformed cells retained a high proportion of type III procollagen, suggesting that either this change is not induced by src protein or else there is a slowly reversible or irreversible step involved. Alternatively, type III procollagen mRNA may be long lived. In contrast, the relative rate of procollagen synthesis in transformed cells was clearly regulated by src protein. Translation of mRNA from cells preincubated at permissive or nonpermissive temperatures revealed that the decreased relative rate can be explained by a simultaneous small decrease in the level of procollagen mRNA and a large increase in mRNA for noncollagen proteins.
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PMID:Mechanisms of Kirsten murine sarcoma virus transformation-induced changes in the collagen phenotype and synthetic rate of BALB 3T3 cells. 627 40

Structural peculiarities of immunoglobulin G (IgG) in cattle with leukemia were studied using the method of dansyl-finger prints and proteolytic fragmentation with pepsin. It is stated that the protein from the blood of leukemic animals differs from the similar IgG subfraction of healthy animals in the amount of peptides: their number is 39 in sick animals, 41--in healthy ones. The studied protein is splitted into three fragments under the effect of pepsin. The molecular mass of F(ab1)2- and Fc1-fragments isolated from the hydrolyzate is 94 and 51 kDa, respectively. Fab-, Fc- and F(ab')2-, Fc'-fragments manifest a complete antigenic identity. The antibody activity is inherent only in the F(ab')2-fragment; it reacts positively in the precipitation test together with monospecific antiserum against IgG, typical of the malignant growth. This confirms a supposition that structural peculiarities of the protein typical of the malignant growth and isolated from the blood of cattle with leukemia depend on changes in the protein Fab-fragment.
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PMID:[Structural features of immunoglobulin G from leukemic cattle]. 642 7

A factor which inhibits the binding of 3H-phorbol-12,13-dibutyrate (PDBu) on different types of cells has been partially purified from human placenta. This factor, phorbol ester binding inhibitory factor (PEBIF), is sensitive to pepsin, but resistant to trypsin, heat and acid (pH 3) treatments and can be precipitated by 80% ethanol with no loss of activity. Inhibition occurs both at 37 degrees C and 4 degrees C and is rapid and reversible. Inhibition on human epithelial cells (FL), on mouse erythroleukaemia cells (FELC clone 19-10) and on rat liver cells (IAR clone 6-1 and clone 20) is non-competitive, whereas on IAR clone 6 and clone 6-7 it is competitive. Differentiation of FELC induced by hexamethylene bisacetamide (HMBA) can be inhibited by 12-O-tetradecanoyl phorbol-13-acetate (TPA) only if TPA-sensitive cells are used, and no inhibition was observed with TPA-resistant cells. PEBIF can also inhibit the differentiation induced by HMBA of TPA-sensitive cells and has no effect on the differentiation of TPA-resistant cells. The extent of inhibition of PDBu binding by PEBIF was similar in these two clones. Like TPA, PEBIF can increase 2-deoxyglucose uptake in mouse fibroblasts (BALB/3T3 cells). Thus, TPA and PEBIF share two biological responses; however, PEBIF failed to mimic other TPA effects, such as induction of Epstein-Barr virus from Raji cells, inhibition of intercellular communication and induction of differentiation of human promyelocytic leukaemia cells (HL-60).
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PMID:A phorbol ester-binding inhibitory factor from human placenta. Partial purification, characterization and biological effects. 659 99

In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.
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PMID:[Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue]. 753 2

Systematic replacement of the P4-P2 subsites of substrate-based human immunodeficiency virus type 1 protease (HIV-1 PR) inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere (Cha-psi [H.E.]-Ala) at positions corresponding to the scissile sites of substrates was carried out. The structure-activity relationship revealed that compounds with the combination of hydrophilic P3 and beta-branched hydrophobic P2 amino acids generally showed strong inhibitory activity against HIV-1 PR. In particular, compounds 4 (Boc-Orn-Val-Cha-psi [H.E.]-Ala-NHBun; Bu(n) = n-butyl, Ki = 11 nM) and 6 (Z-Orn-Val-Cha-psi [H.E.]-Ala-NHBun, Ki = 8 nM) exhibited good enzyme selectivity, possessing no significant inhibitory activities toward closely related aspartic proteases, pepsin, cathepsin D, and renin. As a possible model system for (anti-Mo-MSV/MLV complex (Mo-MSV = Moloney murine sarcoma virus; MLV = murine leukemia virus)) activity was investigated. Both compounds were found to inhibit moderately the focus formation of Mo-MSV/MLV complex in NIH3T3 cells (compound 4, IC50 = 1.8 microM; compound 6, IC50 = 1.0 microM).
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PMID:Studies of human immunodeficiency virus type 1 (HIV-1) protease inhibitors. III. Structure-activity relationship of HIV-1 protease inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere. 800 98


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