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)

We developed an experimental system in which differentiation of teratocarcinoma stem cell is probed by expression of stably introduced exogenous genes. We used chicken delta-crystallin gene (delta gene) and its derivative (Mo delta gene) driven by long terminal repeat (LTR) promoter of Moloney murine leukemia virus (Mo-MuLV). Neither of the genes was expressed in the undifferentiated condition. Differentiation to primitive endoderm induced by retinoic acid (RA) led to expression of delta but not Mo delta, while differentiation to more advanced endodermal cells by RA plus dibutyryl cAMP elicited Mo delta expression in addition to delta. These results are interpreted as a consequence of differential activation/suppression of gene expression through enhancer elements associated with the genes.
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PMID:Exogenous delta-crystallin gene expression as probe for differentiation of teratocarcinoma stem cells. 320 83

L-1210 murine leukemia cells were exposed to prostaglandin D2 (PGD2), 10 micrograms/ml, in culture medium for various time, and subsequent cell growth was observed. More than 24 h exposure to PGD2 was required to inhibit cell growth almost completely. During this period, PGD2 degraded time-dependently into several products. The major product was identified as delta 12-PGJ2 by TLC, UV and mass spectra. When delta 12-PGJ2 was added to cells instead of PGD2, it evoked growth inhibition with much shorter contact time than PGD2. In addition, when the medium containing PGD2 was preincubated at 37 degrees C for 24 h, it elicited growth inhibition with only 6 h contact with cells. Furthermore, when the medium containing PGD2 was changed every 6 h during 24 h exposure time to cells, no significant growth inhibition was observed. These results suggested that PGD2 per se has little, if any, growth inhibitory activity, and delta 12-PGJ2 is an ultimate metabolite exerting growth inhibition. This action appears to be independent of cAMP, since delta 12-PGJ2 was virtually inactive in raising intracellular cAMP levels.
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PMID:delta 12-Prostaglandin J2, an ultimate metabolite of prostaglandin D2 exerting cell growth inhibition. 385 41

2 patients with chronic myelogenous leukaemia developed hypercalcaemia and severe myelofibrosis in the terminal phases of their disease. Hormonal studies excluded the hypercalcaemia being caused by primary hyperparathyroidism or ectopic parathyroid hormone secretion. Its development was unrelated to the phenotype of the blast cells, as assessed by conventional cytochemistry and immunological surface typing. The finding of increased urinary cAMP excretion in 1 of the patients suggests a circulating, nonparathyroid humoral bone resorbing factor with partial biological PTH-activity to be one of the pathogenetic mechanisms responsible for the occurrence of hypercalcaemia in patients with chronic myelogenous leukaemia.
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PMID:Hypercalcaemia in the accelerated phase of chronic myelogenous leukaemia: no relationship to the phenotype of the blast cells. 386 33

This study evaluated the effect of inhibitors of transmethylation on histamine release from rat mast cells and rat basophilic leukemia cells. IgE-mediated histamine release from rat basophilic leukemia cells (RBL-2H3 cells) was inhibited by 3-deazaadenosine (DZA) in the presence of L-homocysteine thiolactone (Hcy) or the combination of adenosine, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), and Hcy in a dose-dependent fashion. There were no significant changes in the cellular cAMP levels by these inhibitors. Histamine release induced by anti-IgE or dextran from normal rat mast cells was also blocked by DZA plus Hcy in a dose-dependent manner. DZA at 10(-3) M in the presence of 10(-4) M Hcy or the combination of 10(-3) M adenosine, 10(-4) M EHNA, and 10(-3) M Hcy inhibited lipid (perhaps phospholipid) methylation into RBL-2H3 cells without affecting choline incorporation. In the presence of 10(-3) M DZA plus 10(-4) M Hcy there was a 170-fold increase in [35S]AdoHcy with the concomitant appearance of 3-deaza-AdoHcy when the cells were incubated with [35S]methionine, thus indicating that these drugs inhibited methylation reaction(s) through the intracellular accumulation of AdoHcy and 3-deaza-AdoHcy. In contrast, histamine release from rat mast cells induced by the calcium ionophore A23187, compound 48/80, polymyxin B, or ATP was not inhibited by these compounds. These results suggest that IgE- or dextran-mediated histamine release involves methylation reactions(s), whereas the other secretagogues bypass this early step.
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PMID:Inhibition of IgE-mediated histamine release from rat basophilic leukemia cells and rat mast cells by inhibitors of transmethylation. 616 84

Down's Syndrome patients are known to be of short stature, prone to infections, autoimmune disease, hypothyroidism, leukaemia, heart defects and later Alzheimer's disease. They tend to have older mothers, like Alzheimer's disease patients. The latter tend to have sibs with either Down's Syndrome or lymphoma/leukaemia. Evidence, looking at 28 Down's Syndrome patients, suggests that multiple food allergies, gluten-gliadin sensitivity or intolerance are causing a coeliac disease-like picture with a malabsorption state for essential vitamins, minerals and severe autoimmune disease. It is hoped that missed gluten-gliadin sensitivity or intolerance with or without coeliac disease will be considered as a cause of abnormal oogenesis and spermatogenesis resulting in trisomy 21 and other aneuploidies. The mechanism most likely is low B1 interfering with sufficient release of cAMP for normal meiosis. Alternatively exorphins and peptides from foods may suppress prostaglandin E1 synthesis, or food sensitivities may alter toxic metal absorption mechanisms, which are thought to play a role in the development of Alzheimer's disease. Adequate vitamin/mineral supplementation, especially B1, prior to conception and in the first trimester is recommended for mothers at risk for DS, especially older mothers and a gluten free diet for those with coeliac disease or gluten-gliadin sensitivity/intolerance. Hopefully this will prevent conception of a DS child, or prevent heart defects/stigmata if one is conceived. DS children should be investigated for the above and commence a food allergy free diet with relevant supplements to meet their needs as early as maximum development.
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PMID:Down's syndrome: nutritional intervention. 624 80

The effects of cyclic nucleotides and PGE1 upon the proliferation of normal granulocyte/macrophage progenitors were examined in in vitro systems and contrasted to the effects of these compounds on (1) granulocyte/macrophage progenitors from the peripheral blood of patients with myeolofibrosis/myeloid metaplasia (MF) and chronic myelogeneous leukemia (CML); and (2) blast progenitors from the peripheral blood of patients with acute myelogenous leukemia (AML) and acute monocytic leukemia (AMoL). Cyclic AMP was found to be a concentration dependent inhibitor of colony proliferation in all systems tested. Cyclic GMP was an inconsistent enhancer of colony proliferation in all systems in a manner which was not clearly concentration dependent. The effect of PGE1 in normal systems was highly variable depending on the culture conditions, but it was generally found to be an inhibitor of colony proliferation. Cyclic AMP, cyclic GMP and PGE1 altered the release of colony stimulating activity from adherent bone marrow cells in a manner opposite to the direct effects of these compounds on progenitor cell proliferation. Abnormalities in response to PGE1 were found in progenitors from patients with CML (deficient inhibition), AMoL (stimulation of proliferation in certain concentration ranges), and MF (enhanced proliferation). Studies on one of the patients with MF indicated that a normally responding population could be defined by density-gradient separation. These data confirm the capacity of these compounds to modulate in vitro proliferation of myeloid progenitors, and suggest that aberrations of response to PGE1 may occur in subpopulations of cells from several myeloproliferative disorders.
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PMID:Modulation of normal and abnormal myeloid progenitor proliferation by cyclic nucleotides and PGE1. 625 72

In the lymphocytes of 20 healthy subjects and 17 patients with chronic lymphatic leukaemia (CLL) the cAMP level was determined before and at different time periods during cell incubation with mitogens (phytohaemagglutinin--PHA, concanavalin A--Con A, and pokeweed mitogen PWM). The experiments demonstrated that PHA-induced lymphocyte proliferation was associated in healthy subjects during the first 10--20 minutes of incubation with a rise in the intracellular cAMP concentration, while the level of cAMP decreased systematically during 30 minutes of incubation with Con A and PWM. Incubation of lymphocytes of the patients with CLL during 30 minutes with PHA, Con A and PWM caused no changes in the low cAMP level in these cells. The obtained results suggest that PHA activation of lymphocytes in healthy subjects is connected with changes in the intracellular concentration of cAMP.
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PMID:[Effect of mitogens on the changes in intracellular cyclic AMP concentration in the lymphocytes of healthy persons and patients with lymphoblastic leukemia]. 627 Sep 47

The pituitary cell line, AtT-20, synthesizes adrenocorticotropic hormone (ACTH) as a glycoprotein precursor that is cleaved into mature hormones during packaging into secretory granules. The cells also produce an endogenous leukemia virus (MuLV) that is glycosylated after translation similar to the glycosylation of the ACTH precursor. Our evidence suggests that the envelope glycoprotein and some precursor ACTH get to the cell surface in a vesicle different from the mature ACTH secretory granule. Viral glycoproteins and ACTH precursor are released from the cells much sooner after synthesis than mature ACTH. Isolated secretory granules do not contain significant amounts of the envelope glycoprotein or ACTH precursor. Exposing cells to 8Br-cAMP stimulates release of mature ACTH four to five fold, but has little effect on the release of the ACTH precursor or the viral glycoproteins. We propose that the viral glycoproteins and some of the ACTH precursor are transported by a constitutive pathway, while mature ACTH is stored in secretory granules where its release is enhanced by stimulation.
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PMID:Two distinct intracellular pathways transport secretory and membrane glycoproteins to the surface of pituitary tumor cells. 627 13

Plasma levels of cyclic AMP and cyclic GMP were determined in 35 guinea pigs for up to 9 days following subcutaneous passage of L2C leukemia cells. Twenty guinea pigs into which normal syngeneic guinea pig thymocytes were passaged served as controls. Cyclic AMP levels in plasma showed little change and were only elevated significantly in test animals on day 9 after passage. In contrast cyclic GMP levels reached a maximum on day 5 after passage of leukemia cells with two to threefold rises over day 1 levels. Increases in leukocyte counts were not observed until day 7 in test animals. Of the other tumour growth indices which were examined, the axillary (draining) node index gave the earliest indication of cell proliferation, with significant elevations on day 3 after passage. The authors conclude that plasma cyclic GMP increases precede increases in white cell counts by at least 2 days, and may reflect an early increase in axillary node growth.
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PMID:Changes in guinea pig plasma cyclic nucleotide levels during the development of a transplantable leukemia. 631 60

A low-molecular-weight (1,400) factor isolated from a human plasma alpha-globulin concentrate by acid-salt dissociation and ultrafiltration inhibits proliferation of mitogen-stimulated T cells and L1210 leukemia cells. The factor (UM05R) inhibits DNA, RNA, and protein synthesis in sensitive cells, acts in G1 of the cell cycle, and appears to suppress mitogen-responsive T cells without an accessory cell requirement. UM05R activity is enhanced by known cAMP-elevating agents and by sulfhydryl compounds. The results of the present study are consistent with the hypothesis that the plasma-derived agent inhibits lympho-proliferation as a result of elevation of intracellular cAMP.
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PMID:Studies with a human plasma-derived immunosuppressive, anti-lymphoma factor. 633 48


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