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 an attempt to define the role of cell adhesion molecules (CAMs) within the bone marrow (BM) microenvironment in normal hematopoiesis and in leukemia development, a novel cell-blotting technique that involved cell adhesion to protein bands after separation by lithium dodecyl sulfate-polyacrylamide gel electrophoresis (LDS-PAGE) and blotting onto polyvinylidene difluoride (PVDF) membrane has been developed. Human BM stromal cell membrane fractions have been prepared from Dexter-type cultures after cell lysis by sonification and differential centrifugations of the sonification contents. The 20,000 g pellets representing membrane fractions have been solubilized by 2% Triton X-100, 0.575% LDS, and 8 mol/L urea in sequential order. The protein extracts are fractionated by LDS-PAGE and screened for CAMs by the new cell-blotting technique. This led to identification of nine protein bands in lanes containing LDS extracts showing adhesion of KG1a (CD34+ progenitor myeloid) cells. Evidence that the BM proteins exhibiting KG1a cell adhesion are novel CAMs is based on the observations that these proteins, in comparison with known CAMs, specifically VCAM-1, CD54, and CD44, show (1) contrasting detergent-solubility properties, (2) different temperature requirement for mediating cell adhesion function, and (3) markedly distinct electrophoretic mobilities. The various cell types tested, notably KG1a, NALM-6, WIL-2, Ramos, HS-Sultan, K562, JY B lymphoblastoid cells, and T lymphoblasts, showed distinctive patterns of binding to different subsets of BM CAMs. These results demonstrate a new approach to studies of molecular mechanisms that may determine specificity of hematopoietic cellular localization within BM microenvironment and may play an important role in controlling hematopoiesis.
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PMID:Discovery of novel hematopoietic cell adhesion molecules from human bone marrow stromal cell membrane protein extracts by a new cell-blotting technique. 751 96

The alterations of the water-electrolyte balance are among the commonest early complications of treatment in children with acute lymphoblastic leukaemia (ALL). A study was carried out in thirteen patients with ALL aged between 1.5 and 14 years. Four had high risk ALL and nine had standard risk ALL. All patients received intravenous epirubicin and vincristine, per os prednisone, allopurinol and bicarbonate, and intrathecal methotrexate and hydrocortisone. Venous blood was drawn before starting therapy and on days second and sixth of treatment in order to assay sodium, potassium, calcium, phosphate, magnesium, albumin, urea nitrogen, creatinine and uric acid concentrations. The following alterations were found: hyponatraemia in 4 cases, hypokalemia in 9, hypomagnesaemia in 9, hypocalcaemia in 11, hypophosphataemia in 9, hypouricemia in 3 and hyperuricaemia in 3 others. None of the patients developed acute renal insufficiency. These abnormalities could be due to the leukaemia itself or appear as a consequence of the remission induction treatment.
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PMID:[Electrolytic changes in children with acute lymphoblastic leukemia during remission induction]. 757 Feb 74

A series of platinum dichloroethylenediamine complexes [PtCl2(R-en)] bearing a side chain on one carbon atom of the ethylenediamine ligand, with or without a functional group on the side chain, have been prepared and investigated for antitumor activity against L1210 leukemia. They were tested both in vitro, with cisplatin-sensitive and resistant cell lines, and in vivo, with cisplatin-sensitive and resistant tumors grafted i.p. in B6D2F1 mice. The rationale for this study was to test how charge, polarity and shape of the R side chain influence antitumor activity. Complexes carrying one or more ammonium groups on the side chain were all inactive. Derivatives with a carbamate function attached by the nitrogen atom, via a methylene group, to the ethylenediamine moiety ('N-bound' carbamate) were highly active in vitro and in vivo. The best results were obtained with these carbamates bearing hydrophobic substituents of intermediate size. Replacement of N-bound by O-bound carbamate or by urea groups led to decreased in vivo activity. Sulfonamide derivatives were all inactive. Good to excellent activities were also recorded for complexes bearing bulky bicycloalkyl substituents, without any functional group, attached to one ethylenediamine carbon atom. Thus, it is the steric features of the side chain rather than its polarity that appear to favor the antitumor activity of the complex. Compared to cisplatin and oxaliplatin, the present complexes do not exhibit advantages in terms of experimental antitumor activities in solid tumor models.
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PMID:Asymmetrically substituted ethylenediamine platinum(II) complexes as antitumor agents: synthesis and structure-activity relationships. 769 13

The peptidoleukotrienes and leukotriene B4, formed from arachidonic acid through the action of 5-lipoxygenase (5-LO), exert a spectrum of biological effects. It has been proposed that potent and selective 5-LO inhibitors will be effective therapy in diseases in which the peptidoleukotrienes and leukotriene B4 have been implicated, such as asthma and arthritis. The novel compound (S)-N-hydroxy-N-(2,3-dihydro-6-phenylmethoxy-3-benzyofuranyl )urea (SB 202235) was evaluated as a selective inhibitor of 5-LO in a cell-free system as well as in various cellular assays. In addition, the potential therapeutic value of SB 202235 was assessed in preclinical models of allergic asthma. The activity of the 5-LO enzyme isolated from rat basophilic leukemia-1 cells was inhibited by SB 202235 in a concentration-dependent manner with an IC50 value of 1.9 microM. Consistent with its ability to inhibit 5-LO, SB 202235 inhibited the production of leukotriene B4 by human monocytes and in human whole blood (IC50 values of 1.5 microM and 1.1 microM, respectively). The selectivity of SB 202235 was confirmed by its lack of effect against several other enzymes and receptors. SB 202235 potently and effectively inhibited the contraction produced by a single concentration of ovalbumin in guinea pig trachea (IC50 = 20 microM) and of anti-IgE in human bronchus (IC50 = 2 microM). SB 202235 (3-30 microM) also inhibited the contraction of guinea pig trachea in response to increasing concentration of ovalbumin. When administered orally (30 mg/kg) to conscious guinea pigs, SB 202235 attenuated antigen-induced broncho-constriction and the subsequent eosinophil influx.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of SB 202235, a potent and selective 5-lipoxygenase inhibitor: effects in models of allergic asthma. 779 Oct 85

In addition to the known 94-kd gelatinase (matrix metalloproteinase 9, MMP-9), HL-60 leukemia cells release a hither-to undescribed 45-kd metalloproteinase into the culture medium. This enzyme cleaves the synthetic substrate Pro-Gln-Gly-Ile-Ala-Gly-Gln-Arg, which represents the cleavage site for collagenases in collagen type I not between isoleucine and alanine--the typical cleavage site for collagenases--but between alanine and glycine. The enzymatic activity was purified through a combination of zinc-chelate-Sepharose column chromatography, precipitation with Fractogel TSK-AF Red and gelatin-Sepharose, and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Microsequence analysis of the NH2-terminus of the purified 45-kd proteinase revealed the sequence Asp-Ile-Ser-Lys-Tyr-Thr-Thr-Thr-, which could not be found in other proteins when searched in several protein data bases. Incubation of the enzyme immobilized on nitrocellulose membranes with polyclonal antibodies to collagenase and stromelysin or gelatinases revealed no cross-reactivity. The proteolytic activity was not increased by treatment with trypsin, 8M urea, acid, or organomercurials. The proteinase, which was inhibited by chemical inhibitors of metalloproteinases, such as phenanthrolene or EDTA, is able to degrade several matrix constituents, such as collagen type IV, fibronectin, gelatin, and proteoglycans. In contrast to all known MMPs, the proteolytic activity of the 45-kd enzyme was not abolished upon incubation with recombinant tissue inhibitors of matrix metalloproteinases (TIMP) 1 or 2. Thus, the novel enzyme may influence extracellular matrix (ECM) turnover in vivo because its activity is not influenced by specific inhibitors of MMPs.
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PMID:Leukemic cells (HL-60) produce a novel extracellular matrix-degrading proteinase that is not inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs). 782 72

Candida is present in the flora of the oral cavity, skin, intestinal tract and vagina, and is also known to be an opportunistic pathogen. Infection with this fungus has been increasing annually along with wide spread use of broad-spectrum antimicrobial agents. The subjects included 95 patients (48 males and 47 females) who had been diagnosed as having had deep-seated candidiasis, among patients autopsied between 1982 to 1991. In regard to annual changes in deep-seated candidiasis, the incidence reached a peak in the 1985 to 1988 period, and thereafter decreased. The number of cases with leukemia as the underlying disease was the largest, 36 (37.9%), followed by malignant lymphoma in 10, and aplastic anemia 5. The number of cases with infection of the stomach was largest, 42 (44.2%), followed by the esophagus in 33 (34.7%), the lung and kidney. The cases with deep-seated candidiasis showed low values of or level of lymphocyte, hemoglobin, CRP, total protein and cholesterol and high values or levels of LDH, urea N, creatinine and total bilirubin. Cases with marked decrease in neutrophils showed no regional infiltration of inflammatory cells in any of the organs infected with Candida. Cases with disseminated candidiasis showed vascular invasion by Candida. The laboratory findings also showed that most of the cases had been undernourished and had high values of CRP which supports the presence of inflammation. Common sites of infection are the esophagus, stomach, and intestinal tract. In the presence of granulocytopenia and immunodeficiency, tissue invasion become severe and associated with vascular invasion.
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PMID:[Retrospective analysis of deep-seated candidiasis among cases autopsied between 1982 to 1991]. 808 55

Between 1980 and 1992, 237 polycythaemic patients aged 65 or more, or with high vascular risk factors were treated with 32P according to a protocol using, or not, maintenance therapy with low-dose hydroxy-urea (500 mg/day). The present follow-up covers 1448 years/patient. Maintenance therapy was seldom discontinued because of blood toxicity or gastrointestinal intolerance, but it was stopped in 20 percent of the cases because monitoring was difficult in very old patients. Maintenance therapy reduced the mean annual 32P dose by at least 50 percent. However, the actual risk of malignant blood diseases (myelodysplasia, acute leukaemia, lymphoma) was similar in the two arms of the protocol: 14 percent at the 10th year. Compared with the French population of the same age-groups, there was no excess of epithelial cancers in both arms. Maintenance therapy did not control platelet counts perfectly. The risk of severe vascular events was identical in both arms; probably no higher than expected at that age and significantly lower than in previously published data. The actuarial survival curves in both groups showed a 50 percent survival of about 11 years, i.e. very near to that of the reference French population (12.5 years) of similar sex and age.
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PMID:[Treatment of polycythemia with 32P with or without hydroxyurea maintenance therapy. Preliminary results in 237 elderly and high vascular risk subjects studied since 1980]. 812 14

The systemic toxicity and efficacy of cisplatin (CDDP) were examined in vitro and in vivo. Procedures were performed before and after the antineoplastic agent was encapsulated into multilamellar liposomes (L-CDDP). In vitro cytotoxicity evaluation in L1210 murine leukaemia and NIH OVCAR human ovarian cancer cells showed IC50 values of 0.14 and 0.05 micrograms/ml with CDDP or L-CDDP, respectively. In vivo, mice injected intravenously with L-CDDP had plasma levels of platinum 4-fold higher than with CDDP. The t1/2 alpha was 2 h and the t1/2 beta exceeded 48 h with L-CDDP; whereas a t1/2 alpha of 15 min and t1/2 beta of 12 h was observed with CDDP. The values of platinum in liver, spleen, kidneys, lungs and heart were substantially higher in L-CDDP-treated compared to CDDP-treated mice. Cytotoxic evaluation of both agents was tested in vitro (murine L1210 leukaemia and NIH OVCAR cell line) and in vivo (male CD2F1 mice). CDDP and L-CDDP showed similar cytotoxicity in tissue culture. At the highest dose given, 12 mg/kg intraperitoneally (i.p.), L-CDDP showed higher antitumour efficacy demonstrated by an increased life span of the mice. The CDDP treatment at the highest dose was lethal to all the tumour bearing mice. The nephrotoxicity in rats (blood urea nitrogen and creatinine evaluation) of L-CDDP administered i.p. was significantly less than with CDDP. In addition, the ability of kidney slices to transport organic anions [para-aminohippurate (PAH)] and consume O2 was substantially decreased in rats treated with free CDDP compared to L-CDDP. Accordingly, the liposomal encapsulation of CDDP attenuates its nephrotoxicity, but allows maintenance of antitumour efficacy and may be a potentially effective modality in clinical settings.
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PMID:Comparative pharmacological, toxicological and antitumoral evaluation of free and liposome-encapsulated cisplatin in rodents. 821 58

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

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.
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PMID:Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity. 826 32


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