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)

The human normal intestinal flora prevents the colonization of exogenous bacteria, maintaining a constant microecology: this property is called "colonization resistance". In leukemia patients antibiotics used for prevention and/or therapy of infectious episodes can alter the intestinal microecology, so that the gut can represent the trigger zone for generalized septicemia. Moreover cytotoxic drugs used in these patients can favour intestinal disturbances. In our study we evaluated the in vitro activity of three commonly used antineoplastic drugs (Daunorubicin, Cytosine arabinoside, Methotrexate) against aerobic and anaerobic intestinal bacteria and Clostridium difficile that is the aetiological agent of pseudomembranous colitis. Daunorubicin proved to be the most active inhibiting, in concentration ranging from 16 to 128 micrograms/ml, 50% of Bacteroides strains and 90% of Clostridium difficile and Enterococci strains tested. Methotrexate showed activity only against some Bacteroides strains, while Cytosine arabinoside had no activity at all. We conclude that in these patients the use of these drugs may represent another factor of risk altering the intestinal flora and so lowering the colonization resistance.
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PMID:[In vitro activity of several cytostatic drugs against aerobic and anaerobic intestinal bacteria]. 653 96

138 patients with neutropenia (PMN's less than 1000), 66 of them with acute myelocytic leukaemia (AML), were hospitalised over a 6-year-period in reverse-barrier isolation. All had skin, orifices and gut decontamination. Fever occurred in 78% of the 216 neutropenic episodes. Overall, the incidence of septicemia during febrile episodes was 10% and the mortality from infection 7%; both figures were identical in the patients with AML and are lower than those normally found in this type of patients. Various factors that might be responsible for this low incidence of severe infections in neutropenic patients have been examined. The microbiological methods used to document infection were identical to those currently used. The severity of the underlying diseases and of neutropenia in the patients with AML was similar to that reported in other series. The measures taken for infection prevention, i.e. reverse-barrier isolation plus skin, orifices and gut decontamination, were not different than those used in many other centers, although their strict application in a small specialized unit might partially explain these favourable results. In addition the outcome of infection was analysed in relation to the response to treatment of the underlying disease. The mortality due to infection in patients with a tumor responding to chemotherapy was only 4% but was 45% in patients with end-stage malignant diseases. These results suggest therefore that infection in patients whose malignancy respond to treatment can be efficiently controlled by prompt empiric broad spectrum antibiotic therapy, and failures of antiinfectious treatment are mostly observed in patients with advanced cancer.
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PMID:Low morbidity and mortality from infection in neutropenic patients, a possible result of multiple measures of infection prevention. 658 32

A survey on the clinical use of medical isolators was undertaken by sending out a questionnaire to the major medical and pediatric oncology services in Japan. As of December, 1981, laminar-air-flow rooms (LAFR) were installed in hospital rooms of 79 institutions. To date, 68 patients with leukemia, 12 with malignant lymphoma and 10 with aplastic anemia have been treated in LAFR for the purpose of bone marrow transplantation. So far, 501 patients with leukemia, 24 with malignant lymphoma and 14 with solid tumor have been treated in LAFR for the purpose of intensive chemotherapy. A variety of items as to the clinical use of medical isolators, such as type of LAFR, decontamination of isolators, protective clothing, food and gut sterilization and attending staff were surveyed. There remain many problems in the use of medical isolators, such as the high cost of establishing and maintaining a bioclean system, the shortage of nursing staff, the lack of space and accessory equipment and so on. Nevertheless, the author will continue to recommend isolation with a physical barrier, protective clothing for attending staff, pathogen-free food and oral prophylactic anti-microbial agents.
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PMID:Clinical use of bioclean rooms in Japan with special reference to medical isolators. 683 59

We studied binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells. We found two types of serotonin binding protein in RBL cells. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 X 10(-6) M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD1 = 4.5 X 10(-8) M; KD2 = 3.9 X 10(-6) M) did not bind to Con A. Moreover, binding of [3H]serotonin to protein of peak I was sensitive to inhibition by reserpine, while binding of [3H]serotonin to protein of peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract peak I than peak II protein. Neither peak I nor peak II protein resembled the serotonin binding protein (SBP) that is found in serotonergic neurons of the brain and gut. Electron microscope radioautographic analysis of the intracellular distribution of [3H]serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules. No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but peak I protein may be associated with the granular membrane while peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.
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PMID:Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of [3H]serotonin. 711 96

Levodopa and dopamine demonstrate significant antitumor activity in several experimental systems. We have prepared the nonneurotoxic dihydroxybenzylamine (DHBA) analogs 2,3-DHBA, 3,4-DHBA, and 2,5-DHBA and the trihydroxy derivatives 2,3,4- and 3,4,5-trihydroxybenzylamine. These analogs demonstrated significant and reproducible antitumor activity in the ip P388 and L1210 lymphocytic leukemias. This activity was markedly increased when the drugs were given by multiple injections three times daily for 4 days. 3,4-DHBA and 2,3-DHBA resulted in 30% and 20% long-term survivors, respectively. There was a selective inhibition of thymidine incorporation and a relatively lesser effect on uridine and leucine incorporations. Inhibitory concentrations were between 0.1 and 1.0 mM. The trihydroxy derivatives were more potent, with inhibitory concentrations between 0.01 and 1.0 mM. Furthermore, the trihydroxy derivatives were also able to inhibit the incorporation of uridine and leucine as well as thymidine. The para derivative, 2,5-DHBA, although a potent inhibitor in vitro, was completely inactive in vivo. When L1210 and P388 tumor-bearing animals were given radioactive labeled thymidine in vivo following the administration of drugs. a selective inhibition of thymidine incorporation by tumor cells was observed, with essentially no effect on gut or bone marrow. Doses greater than 200 mg/kg completely suppressed the incorporation of radioactively labeled thymidine by tumor cells 1 hour after administration of drug. A similar dose response was observed in the more slowly growing P388 leukemia, suggesting that the antitumor effect did not strongly correlate with rate of the tumor. Since levodopa and dopamine are currently being evaluated in patients with metastatic melanoma, the availability of analogs with enhanced antitumor activity and broader antitumor spectrum are of interest.
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PMID:Levodopa and dopamine analogs: dihydroxy and trihydroxybenzylamines as novel quinol antitumor agents in experimental leukemia in vivo. 727 19

T-cell epitopes are now well understood as amino-acid nonamers binding to major histocompatibility complex molecules. Powerful methods have been developed for their identification through screening of recombinant and synthetic peptides. Multiple epitopes from a single protein are valuable for detecting T-cell reactivity in disease, currently in human immunodeficiency virus infection, and in the future in autoimmune disease. Surprises are likely to be encountered while exploring the T-cell repertoire in this way, such as positive as well as negative selection of self-reactivity. T-epitopes are likely to find important applications in therapy, particularly in down-regulation of the immune response. Multiple mechanisms of down-regulation appear to operate, among which bystander suppression by TGF beta-producing T-cells from the gut is of great current interest.
Leukemia 1993 Aug
PMID:Where are peptides taking us in T-cell biology? 768 73

The Myb-Ets oncoprotein encoded by the E26 avian leukaemia virus represents a fusion of two transcription factors which cooperate in transforming multipotent haematopoietic progenitors (MEPs) in vitro and in vivo. Previous studies with a temperature sensitive mutant in ets (ts1.1 E26) have suggested that the Ets part of the Myb-Ets fusion protein blocks multilineage differentiation of transformed MEPs, by regulating specific target genes. Using this system in a differential screening approach we have now identified a new gene, called rem-1, as a target for the E26 virus. Following shift of ts1.1 mutant transformed cells to the nonpermissive temperature a decreased expression of rem-1 was observed which increased upon downshift. The finding that this reexpression did not require new protein synthesis suggests that the Ets component of the fusion protein directly regulates rem-1 transcription. Rem-1 is related to a family of EF-hand-containing calcium-binding proteins that are predominantly expressed in the brain and in retinal cells. This family includes recoverin and visinin, proteins that have been implicated in regulating photoreception. Rem-1 is likewise expressed in these tissues but in addition in haematopoietic cells and in the gut. Enforced expression of rem-1 in ts1.1-transformed MEP cells, using a retroviral vector, showed that this gene is not sufficient to block their differentiation, but that it may provide them with a growth advantage.
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PMID:Rem-1, a putative direct target gene of the Myb-Ets fusion oncoprotein in haematopoietic progenitors, is a member of the recoverin family. 770 Jun 27

Mouse thymus-leukemia antigen (TL), like other major histocompatibility complex (MHC) class I-b antigens, displays signs of a specialized function. It is normally expressed at high levels on immature thymocytes and at moderate levels on gut epithelium and activated mature T cells. A promoter/enhancer region unique among class I genes accounts for this narrow range of tissue distribution. Like most other class I molecules, TL is dependent upon endogenous beta 2-microglobulin (beta 2m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absence of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA and RMA-S cells. In bulk transformants, TL expression is higher in TAP2-RMA-S cells than in wild-type RMA cells, and is not elevated by incubation at reduced temperatures or exposure to exogenous beta 2m. Analysis of immunoprecipitated molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates that TL is processed normally in RMA-S cells and is associated with beta 2m both intracellularly and at the cell surface. However, TL heavy chains expressed on the cell surface in the absence of TAP2 are cleaved to a predominant 38 kDa fragment, presumably the result of an altered conformation that renders TL more susceptible to proteolysis. These results suggest that while TL may normally acquire TAP2-dependent peptides, this class I-b molecule does not require them for efficient export to, and stable expression at the cell surface.
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PMID:Surface expression of beta 2-microglobulin-associated thymus-leukemia antigen is independent of TAP2. 773 70

The clinical efficacy of assays for Candida albicans antigens by latex agglutination and for antibodies by indirect haemagglutination were prospectively evaluated in the diagnosis of invasive Candida infections in 38 children suffering from acute leukaemia or other malignant disease. The controls were 74 other patients without any malignancy; 72 of these had no signs or symptoms of fungal infections, but 2 had an invasive C. albicans infection. During a period of 21 months, 302 serum samples were tested by both assays, and the results were compared with clinical and other microbiological data. Invasive fungal infection was diagnosed on clinical grounds in 2 of the immunocompromised children, and periodic gut colonization was demonstrated in 11 of 36 (31%) children in this group. Positive Candida antigen was detected in 14 patients (37%) and a positive antibody titre in 7 patients (18%). Colonization was not correlated with antigen or antibody titre. Compared with the presence of invasive fungal infection, the antibody assay detected all four infections, whereas the antigen assay detected one of the two C. albicans septicaemias. Although the Candida antibody assay performed well, a detectable change in antibody titres appeared only slowly. Thus it was of no clinical help when antifungal treatment was to be considered. Follow-up of antibody titres, however, gave confirmation of the presence of fungal infection as well as the response to antifungal treatment.
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PMID:Prospective evaluation of Candida antigen and antibody assays for detection of Candida infections in children with malignant disease. 748 32

Mad is a basic region helix-loop-helix leucine zipper transcription factor which can dimerize with the Max protein and antagonize transcriptional activation by the Myc-Max transcription factor heterodimer. While the expression of Myc is necessary for cell proliferation, the expression of Mad is induced upon differentiation of at least some leukemia cell lines. Here, the expression of the mad gene has been explored in developing mouse tissues. During organogenesis in mouse embryos mad mRNA was predominantly expressed in the liver and in the mantle layer of the developing brain. At later stages mad expression was detected in neuroretina, epidermis, and whisker follicles, and in adult mice mad was expressed at variable levels in most organs analyzed. Interestingly, in the skin mad was highly expressed in the differentiating epidermal keratinocytes, but not in the underlying proliferating basal keratinocyte layer. Also, in the gut mad mRNA was abundant in the intestinal villi, where cells cease proliferation and differentiate, but not in the crypts, where the intestinal epithelial cells proliferate. In the testis, mad expression was associated with the completion of meiosis and early development of haploid cells. In cell culture, Mad inhibited colony formation of a mouse keratinocyte cell line and rat embryo fibroblast transformation by Myc and Ras. The pattern of mad expression in tissues and its ability to inhibit cell growth in vitro suggests that Mad can cause the cessation of cell proliferation associated with cell differentiation in vivo.
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PMID:Expression of the mad gene during cell differentiation in vivo and its inhibition of cell growth in vitro. 789 82


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