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 rat basophilic leukemia cells (RBL-2H3), a tumor analogue of mast cells, the aggregation of IgE receptors initiates increase in the intracellular concentration of calcium ([Ca2+]i), monitored with the fluorescent Ca probe fura-2, and finally results in histamine secretion. In cell suspensions, however, the fluorescence gradually increases due to leakage and exocytosis of the dye. A superfusion system was developed to overcome these problems and [Ca2+]i was calculated from the ratio of fluorescence intensities at 505 nm of fura-2 excited at 340 and 380 nm. Histamine and beta-N-acetylglucosaminidase in granules are released during exocytosis, and both substances in the superfusates were determined simultaneously. This system is useful for studies on the relationships of cell stimulation, changes in second messengers, and final responses.
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PMID:Simultaneous determination of intracellular calcium concentration and histamine secretion in rat basophilic leukemia cells (RBL-2H3). 171 50

We combined fluorescence labeling, digital image processing, and micromanipulation to investigate the intracellular events induced by inflicting a mechanical stress on rat basophilic leukemia cells. Our findings were as follows: 1. Most cells displayed a localized calcium rise in response to micropipet aspiration. This represented an average threefold increase as compared to resting level, and it was observed during the first 10 s following aspiration. A slow return to initial level occurred within about 3 min. Further, this calcium rise involved a mobilization of intracellular stores, since it was not prevented by adding a calcium chelator into the extracellular medium. 2. All micropipet-aspirated cells displayed a local accumulation of microfilaments, with a preferential localization in the cell protrusions or near the pipet tips. 3. No absolute correlation was found between the localization of calcium rise and cytoskeletal accumulation. 4. Cell deformability was decreased when intracellular calcium was maintained at a constant (high or low) level with ionomycin and/or EGTA. It is concluded that cells have a general ability to respond to mechanical stimulation by a coordinated set of events. More parameters must be studied before the mechanisms of cell shape regulation are fully understood.
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PMID:Localization of calcium and microfilament changes in mechanically stressed cells. 171 50

MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.
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PMID:Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s. 171 95

We report the purification from a rat natural killer (RNK) large granular lymphocyte leukemia of a 32-kD granule protein that induces rapid DNA fragmentation and apoptosis. The protein, which we have called "fragmentin," was capable of causing DNA from intact YAC-1 cells to be cleaved into oligonucleosomal-sized fragments and producing severe chromatin condensation within 1 h. Amino acid sequence of tryptic peptides indicated that fragmentin was highly homologous to the NK and T cell granule serine proteases RNK protease 1 and mouse cytotoxic T cell protease I (CCPI)/granzyme B. Preincubation with the serine esterase inhibitor 3,4-dichloroisocoumarin blocked fragmentin-induced DNA damage, but had no effect on cytolysin. Fragmentin activity against four lymphoma target cells was completely dependent on the presence of cytolysin. Fragmentin produced rapid membrane damage as well as DNA fragmentation at nonlytic cytolysin doses, suggesting that fragmentin activity was not limited to its effects on the nucleus. Fragmentin and cytolysin activity were completely inhibited by EGTA, indicating the process was Ca2+ dependent. A role for cytolysin in endocytosis of fragmentin was suggested by the observation that treatment of YAC-1 with cytochalasin B or sodium azide and 2-deoxyglucose blocked DNA fragmentation but not cytolysin activity. A 30-kD N alpha-CBZ-L-lysine thiobenzyl esterase, which copurified with fragmentin, was inactive on its own but was able to synergistically amplify the DNA damage induced by fragmentin in the presence of cytolysin. Fragmentin activity was not dependent on protein synthesis, as cycloheximide treatment of YAC-1 cells did not prevent DNA damage. We postulate that fragmentin is the molecular mediator of NK cell-mediated DNA fragmentation and apoptosis.
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PMID:A natural killer cell granule protein that induces DNA fragmentation and apoptosis. 173 16

Antigenic stimulation of rat basophilic leukemia (RBL-2H3) cells, a tumor mast cell line, is associated with an increase in intracellular free Ca2+ concentrations ([Ca2+]i) and membrane polarization. We recorded whole cell and single-channel currents through the inwardly rectifying K+ channel, a major resting conductance of cells, using the patch-clamp technique, and we examined interactions between channel activity and [Ca2+]i. With 10 microM Ca2+ in the pipette, the amplitude of whole cell currents gradually declined within 5 min to 48 +/- 13% of that immediately after rupture of the patch membrane, in the presence of 1 mM ATP which minimized intrinsic rundown. In inside-out patches, activity of the channel was reduced by increasing the concentration of Ca2+ in the internal medium, both in the presence and absence of 1 mM ATP, with no apparent change in single-channel conductance. Time-averaged mean current activity in inside-out patches in the presence of 5 microM Ca2+ was less than 50% of that with Ca2+ of 100 nM or less. These results suggest that a rise in [Ca2+]i leads to a closure of the inwardly rectifying K+ channel. In some inside-out patches, inward currents characterized by burst composed of rapid transitions between open and closed states were observed (flickering currents). Single-channel properties of the flickering currents are similar to the inwardly rectifying K+ channel except for kinetics (single-channel conductance of 24.5 +/- 7.9 pS, inward rectification, and permeability to K+).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium-dependent inactivation of inwardly rectifying K+ channel in a tumor mast cell line. 173 36

The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less than 2.74 mmol/l), lactate dehydrogenase (LDH) value of up to 1.5 x the normal upper limit, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone and gastrointestinal tract, and neither ascites nor pleural effusion. Skin and pulmonary lesion(s) may be present. In case of less than 5% abnormal T-lymphocytes in PB, at least one of histologically-proven skin and pulmonary lesions should be present. (2) Chronic type, absolute lymphocytosis (4 x 10(9)/l or more) with T-lymphocytosis more than 3.5 x 10(9)/l, LDH value up to twice the normal upper limit, no hypercalcaemia, no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion. Lymphadenopathy and involvement of liver, spleen, skin, and lung may be present, and 5% or more abnormal T-lymphocytes are seen in PB in most cases . (3) Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and histologically-proven lymphadenopathy with or without extranodal lesions. (4) Acute type, remaining ATL patients who have usually leukaemic manifestation and tumour lesions, but are not classified as any of the three other types. A total of 818 ATL patients with a mean age of 57 years, newly diagnosed from 1983 to 1987, were analysed by this criteria. There were 448 males and 370 females, and 253 were still alive with a median follow-up time of 13.3 months from diagnosis, while 565 were dead with a median survival time (MST) of 5.4 months. MST was 6.2 months for acute type, 10.2 months for lymphoma type, 24.3 months for chronic type, and not yet reached for smouldering type. Projected 2- and 4-year survival rates were 16.7% and 5.0% for acute type, 21.3% and 5.7% for lymphoma type, 52.4% and 26.9% for chronic type, 77.7% and 62.8% for smouldering type, respectively. Distinct clinical features and laboratory findings of each clinical subtype are described.
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PMID:Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). 175 70

The effect of calcium antagonist verapamil on the uptake and efflux of Etoposide (VP16), a semi-synthetic derivative of podophylotoxin and a broad spectrum antineoplastic agent, has been investigated and compared in sensitive (UM-UC-2) and resistant (UM-UC-9) human bladder cancer cells, and L1210 leukemia cells, by using both radioisotope (3[H]-VP16) liquid scintillation and high performance liquid chromatography assay with electrochemical detection. The uptake of VP16 was rapid in all three cell lines, showing an initial rapid linear phase followed by a second slower phase, but at steady state the ratios of intracellular to extracellular VP16 concentrations were only 0.004-0.006. No significant difference in drug uptake was observed in sensitive UM-UC-2 and resistant UM-UC-9 cells at all concentrations studied. Verapamil at a concentration of 10 microM enhanced the intracellular VP-16 levels in all sensitive and resistant cell lines. The increments were 21.5% for UM-UC-2, 11.8% for UM-UC-9, and 31.0% for L1210 cells after 30 minutes incubation with 1 microM VP16. A slower efflux of VP16 was observed in verapamil treated cells in all three cell lines. There was a small increase in the nonexchangeable components in verapamil treated cells, although only 5-10% of VP16 was retained. No peak other than that of VP16 was detected in the HPLC chromatogram of extracts from both cell pellet and influx or efflux medium.
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PMID:Effect of verapamil on the uptake and efflux of etoposide (VP16) in both sensitive and resistant cancer cells. 175 30

Human interleukin-2 receptor cDNA was transfected into mouse fibroblast cells (L929) by using DNA-calcium phosphate coprecipitation method. Results from RNA dot-blot hybri dization, FITC-IL-2 fluorescent staining assay and anti-Tac specific rossette test demonstrated that the product of human interleukin-2 receptor cDNA in L929 cells is able to bind IL-2 and anti-Tac antibody. Moreover, the abnormal expression of IL-2R gene in T-cell leukemia cell lines such as Jukat cells and Molt-4 cells was analyzed and discussed.
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PMID:[Studies of the expression of human interleukin-2 receptor cDNA in mammalian cells]. 176 Jan 93

Abelson Leukemia Virus-transformed mouse cell lines with an early pre-B phenotype carry partially rearranged or unrearranged Ig-H genes and consequently do not express intact IgM-H protein (mu protein). Such early mu- pre-B cells express an intracellular protein complex of the pre-B cell specific 22 kDa protein lambda 5 and a 16 kDa protein designated p16. Late pre-B cell lines which carry a rearranged IgM-H chain gene in which a continuous translational reading frame has been established in the fused V-D-J element express intact mu-protein, which forms an intracellular complex with lambda 5 and p16. We show here that both the lambda 5/p16 or the mu/lambda 5/p16 complexes can be immunoprecipitated from lysates of cells surface labeled with 125I. Thus early pre-B cells express the lambda 5/p16 complex on the cell surface in the absence of mu protein, while mu+ late pre-B cells express a surface mu/lambda 5/p16 complex. To investigate a possible signal transduction function of the lambda 5/p16 and mu/lambda 5/p16 complexes on the surface of pre-B cell lines we measured the changes in intracellular free Ca2+ after treatment of cells with anti-lambda 5 or anti-mu antibodies. Two mu- early pre-B cell lines showed a rapid and transient increase in intracellular free Ca2+ when incubated with anti-lambda 5 antibodies but not when incubated with anti-mu, while the mu+ late pre-B cell line CB32 showed a rapid and transient increase in intracellular Ca2+ after incubation with anti-lambda 5 or anti-mu. These results show that both the lambda 5/p16 and the mu/lambda 5/p16 cell surface protein complexes can transduce an external signal to the inside of the cell, which implicates these complexes in the regulation of pre-B cell physiology.
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PMID:The immunoglobulin light chain related protein lambda 5 is expressed on the surface of mouse pre-B cell lines and can function as a signal transducing molecule. 176 Apr 7

Four cases of metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL) are reported. Serum calcium was at high levels, 15.4-19.4 mg/dl (normal range 8.4-10.4 mg/dl). In our cases, metastatic calcification was detected by v. Kossa's silver nitrate method for calcium in tubules of kidneys (100%), pulmonary alveolar septa of lungs (100%), myocardium (75%), muscular layer of stomach (50%), lower portion of aortic media (50%), gastric mucosa (25%), testicular tubules (25%), and in the liver (25%). Scattered osteoclasts were seen around the cortex of the bone. Therefore, hypercalcemia in ATLL may have been caused by bone-resorption-stimulating factors which promote differentiation of osteoclast cells, resulting in calcium increase in the serum.
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PMID:Metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL). 176 85


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