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)

Immunoglobulin G (IgG) and albumin (Alb.) were measured in the cerebrospinal fluid (CSF) of 14 children with acute lymphoblastic leukaemia (ALL), with and without leukaemic infiltration of the central nervous system (CNS). The following indexes: (formula; see text) were calculated and used to express a protein profile of the CSF. This profile was found to be inflammatory-like in 10 children (71%) and normal in 4 (29%). The first two indexes, that reflect a local synthesis of IgG correlated significantly (r = 0.823; p less than 0.001). The follow-up made in five children showed a relationship between clinical course and local IgG synthesis.
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PMID:Neuroimmunitary profile estimation in cerebrospinal fluid and its importance in childhood acute lymphoblastic leukaemia. 275 78

Determination of amsacrine plasma protein binding by both equilibrium dialysis and ultracentrifugation gave similar results and indicated that amsacrine is highly bound (approximately 97%) in human plasma. This binding is independent of amsacrine concentration over the range 1-100 mumol litre-1, but is very sensitive to plasma pH and, to a lesser extent, to temperature. Approximately 20% of the drug appeared to be covalently bound to plasma proteins. Amsacrine was bound by all plasma proteins investigated including albumin, alpha 1-acid glycoprotein and various gamma-globulins. The binding to albumin appeared to occur by two processes, a saturable process at a single site with a KD of 13.9 mumol litre-1 and a non-saturable process. Despite differences in individual protein concentrations, no significant difference was observed in the unbound amsacrine fraction in plasma from patients receiving this drug for treatment of acute myelogenous leukaemia and plasma from healthy individuals.
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PMID:The binding of amsacrine to human plasma proteins. 287 19

Among 569 patients with newly diagnosed AML, 16% died in the 4 weeks following initiation of remission induction therapy. Eight pretreatment characteristics were found to be independently associated with 4-week survival: performance status, bilirubin, age, neutrophil count, fibrinogen, albumin, hemoglobin, and creatinine. A model incorporating these characteristics prospectively stratified a separate group of 198 patients into two comparably sized groups differing substantially in both 4-week survival rates (71% (95% confidence limits, 61-80%) vs. 91% (95% confidence limits, 83-96%] and in survival rates throughout remission induction. Characteristics associated with failure to survive 4 weeks were unassociated with resistance to therapy. This suggests that patients who fail to survive induction are qualitatively different than patients who survive induction but exhibit resistance to treatment. Different therapeutic strategies might be appropriate in the two groups. The model presented here can be used to identify patients at increased risk of death during remission induction.
Leukemia 1989 Apr
PMID:Prediction of survival during induction therapy in patients with newly diagnosed acute myeloblastic leukemia. 292 76

The plasma membrane of murine erythro-leukemia (MEL) cells contains a 140-kD protein that binds specifically to fibronectin. A 125I-labeled 140-kD protein from surface-labeled uninduced MEL cells was specifically bound by an affinity matrix that contained the 115-kD cell binding fragment of fibronectin, and specifically eluted by a synthetic peptide that has cell attachment-promoting activity. The loss of this protein during erythroid differentiation was correlated with loss of cellular adhesion to fibronectin. Both MEL cells and reticulocytes attached to the same site on fibronectin as do fibroblasts since adhesion of erythroid cells to fibronectin was specifically blocked by a monoclonal antibody directed against the cell-binding fragment of fibronectin and by a synthetic peptide containing the Arg-Gly-Asp-Ser sequence found in the cell-binding fragment of fibronectin. Erythroid cells attached specifically to surfaces coated either with the 115-kD cell-binding fragment of fibronectin or with the synthetic peptide-albumin complex. Thus, the erythroid 140-kD protein exhibits several properties in common with those described for the fibronectin receptor of fibroblasts. We propose that loss or modification of this protein at the cell surface is responsible for the loss of cellular adhesion to fibronectin during erythroid differentiation.
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PMID:The fibronectin receptor on mammalian erythroid precursor cells: characterization and developmental regulation. 293 41

Trimetrexate, an investigational antifol, has been associated with marked variability in drug tolerance among patients. The agent is extensively protein bound, and hepatic biotransformation plays a major role in its elimination. In early phase II testing, nine of 15 patients who experienced life-threatening or fatal toxic effects from trimetrexate had albumin levels less than or equal to 3.5 g/dL prior to treatment. This prompted a review of the data base on 272 patients entered in phase I clinical trails. The incidence of severe or life-threatening anemia, leukopenia, neutropenia, thrombocytopenia, mucositis, and hepatic toxic effects during the first course of trimetrexate was analyzed according to dose, schedule, prior treatment, and baseline protein and albumin levels. The schedules using doses given by short infusions of 30-60 minutes daily for 5 days or weekly for 3 weeks were generally associated with higher incidence of toxic effects than the schedules using doses given every other week by short infusions or those using continuous infusion. The occurrence of leukopenia and mucositis was dose related. Patients with baseline albumin levels less than or equal to 3.5 g/dL had higher incidence of all types of severe or life-threatening toxic effects than those with albumin levels greater than or equal to 3.6 g/dL, and the differences were significant for the development of anemia, thrombocytopenia, and mucositis. Similar correlations were noted for pretreatment protein levels less than or equal to 6.0 g/dL. The small cohort of patients with leukemia experienced substantial toxic effects and tended to have low protein and albumin levels. Performance status and prior therapy did not emerge as strong predictors of severe toxic effects in the univariate analysis. Multivariate analysis confirmed that the type of cancer (leukemia vs. solid tumor), dose, schedule, and baseline albumin level were significant and independent predictors of severe and life-threatening toxic effects in the phase I patient population. Multivariate analysis including only patients with solid tumors indicated that albumin level, dose, and schedule remained significant predictors of toxic effects. Since normal liver function as reflected by bilirubin and transaminase values were a requirement for eligibility, the results suggest that albumin and protein levels may provide a more sensitive index of hepatic function. Patients with hypoalbuminemia and hypoproteinemia are at increased risk of experiencing severe or life-threatening toxic effects from trimetrexate and should be treated cautiously.
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PMID:Correlates of severe or life-threatening toxic effects from trimetrexate. 297 17

L-Asparaginase (ASNase), a drug widely used in the treatment of acute lymphoblastic leukemia, has been reported to decrease serum T4-binding globulin (TBG) levels, while results of serum albumin determinations were conflicting. This effect in vivo has been attributed to depressed liver protein synthesis, but this hypothesis has not been proved. To investigate this problem, human hepatoma (Hep G2) cells were continuously labeled for 4 h with 100 microCi/ml [35S]methionine in the absence or presence of graded amounts of ASNase (from 0.1 nM to 0.1 mM). Media and cell lysates were collected, immunoprecipitated with antialbumin or anti-TBG serum and protein A, and submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were sliced, and the radioactivity was counted in a beta-counter. A dose-dependent inhibition of TBG and albumin biosynthesis (as well as of total protein synthesis) was demonstrable, but TBG appeared to be more sensitive to the action of the drug. In fact, TBG biosynthesis was reduced by 8% with 0.1 nM ASNase, while an effect on albumin was observed only at 1 nM ASNase; 50% inhibition was obtained with 30 nM ASNase in the case of TBG and with 800 nM in the case of albumin. At the highest concentration (0.1 mM), TBG biosynthesis was reduced by 94%, and albumin biosynthesis by 75%. ASNase also proved to have a time-dependent effect, as assessed by the measurement of radioimmunoassayable TBG in the media from Hep G2 cells grown in the presence of 10 nM ASNase for 1-4 days. The TBG concentration was progressively reduced, by 40% after 1 day to 85% after 4 days. In pulse-chase experiments, a reduction of total (intracellular plus secreted) immunoprecipitable TBG and, to a lesser extent, albumin was observed, suggesting that the drug also affected the catabolism of newly synthesized proteins. These results provide the first in vitro evidence that ASNase actually inhibits TBG biosynthesis. This effect is not specific for TBG, but this protein appears to be more susceptible than albumin to ASNase action. This can explain why in patients treated with ASNase for leukemia, a decrease in serum TBG concentrations has not always been associated with a reduction in serum albumin levels.
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PMID:Effect of the antileukemic agent L-asparaginase on thyroxine-binding globulin and albumin synthesis in cultured human hepatoma (HEP G2) cells. 301 70

The study investigates clinical nutrition of oncological patients as an essential adjuvant component in the whole therapeutical concept. The main subject of the study was the transfer of nutritional concepts which were developed in non-malignant diseases to oncological patients. We defined the homeostasis of patients by biochemical and biophysical parameters in blood (osmolality, Na, K, total protein, albumin, triglycerides, NEFA, glucose, lactate, creatinine, urea, total nitrogen, amino acids) and urine (volume, osmolality, Na, K, creatinine, urea, total nitrogen, and amino acids). Of special interest was the homeostasis of nitrogen, which was characterized by the loss of nitrogen and nitrogen balances. 10 patients with either transplantable panmyeolopathy or leukemia were investigated including a phase of immunsupressive treatment by total body radiation and cytostatic treatment. Parenteral nutrition was made with amino acids (1 g/kg/d), carbohydrates (6.5 g/kg/d) and fat (1 g/kg/d). During the preparatory phase nutrition was interrupted for two consecutive days because high amounts of electrolyte solution with up to 6 1/day were needed to protect the kidney. The period of investigation covered the complete period of treatment which endured up to three months. The essential result was the achievement of a constant body weight which decreased drastically under the conventional treatment without optimized nutrition. The homeostasis remained unchanged inspite of the fact that great changes occurred individually. Nitrogen balance and nitrogen loss demonstrate the strong influence of immun-suppresive treatment with N-losses of up to 20 g per day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Adjuvant parenteral nutrition in chemo- and radiotherapeutic measures in hematology]. 309

There were 72 patients (19 with hepatic failure, 10 with fulminant hepatitis, eight with paraquat poisoning, eight with rheumatoid arthritis, five with myasthenia gravis, four with hyperlipidemia, four with systemic arteriosclerosis including brain infarction, three with pemphigus vulgaris, two with multiple myeloma, two with systemic lupus erythematosus, two cases non-specific Ig-G antibody, two cases medication with an anticancer drug, one with multiple sclerosis, one with Crohn's disease with amyloid kidney and one with chronic myeloblastic leukemia) treated by plasma exchange in the Kidney Center, Tokai University School of Medicine from Jan. 1983 to Dec. 1986. We performed plasma exchange using fresh frozen plasma in 40 cases and Lactate-Ringer's solution containing albumin (4.0-5.0%) in 20 cases as the replacement fluid. In 17 cases, we performed double filtration plasma exchange with the recycle system and no replacement fluid. Although PE therapy did not constitute a basic therapy for hyperlipidemia, pemphigus vulgaris, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus, it was effective in relieving severe clinical symptoms. At the present time, conventional plasma exchange does not improve the survival rate of patients with hepatic failure and fulminant hepatitis. Developments of a new artificial liver support apparatus and identity of many toxic substances in hepatic failure are necessary. No hypotension, hypovolemic shock or other significant complications were experienced.
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PMID:Clinical reports on plasma exchange in the Kidney Center, Tokai University School of Medicine. 344 83

The pharmacokinetics of amsacrine have been studied after the first and third infusions (200 mg . m-2) in 10 patients receiving combined chemotherapy for the treatment of acute myelogenous leukaemia (AML). Postinfusion amsacrine elimination was best described by a biexponential expression with a mean t1/2 alpha of 0.8 h and a terminal t1/2 beta of 5.3 h. After the third infusion there was a significant reduction (P less than 0.05) in the plasma clearance (Cl) and a prolongation of the terminal half-life (t1/2 beta) (P less than 0.01), but no change in the initial half-life (T1/2 alpha) or volume of distribution (Vd). No significant overall changes were recorded in any of the biochemical indices of renal or hepatic function between the first and third infusions, but the patient who exhibited the largest reduction in Cl showed a marked increase in AST levels and a reduction in albumin concentration. Two distinct groups were apparent after the first infusion, patients with a Cl greater than 294 and those with a Cl less than 208 ml . h-1 . kg-1. The latter patients were significantly older (P less than 0.05), and four of the five had subnormal albumin concentrations. Urinary determination of amsacrine indicated that renal elimination plays a minor role in the total clearance of this drug. Amsacrine was also found to be highly bound to plasma proteins (96.4%-97.7%), but changes in binding were not responsible for the reduced Cl and prolonged t1/2 beta observed between the first and third infusions. We suggest that the elimination of amsacrine may be susceptible to small changes in hepatic function, perhaps due to the high amsacrine concentrations (5-18 mumol . l-1) achieved with this regimen, which may be approaching saturation of the capacity for hepatic elimination.
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PMID:Pharmacokinetics of amsacrine in patients receiving combined chemotherapy for treatment of acute myelogenous leukemia. 385 88

Ten children affected by acute lymphoblastic leukaemia without CNS involvement were treated with a CNS prophylaxis protocol. Intrathecal methotrexate and CNS irradiation (60Co) administered at different times both induced an increase in blood-CSF barrier permeability to serum proteins (albumin, IgG, alpha 2 macroglobulin). The relationship between permeability coefficients of proteins was analysed by theoretical porous or vesicular blood-CSF barrier models. The analysis indicated that both therapeutic procedures affect endothelial pinocytosis. An increase in radius of pinocytotic vesicles from 400 to 1500 A seemed the most relevant change. The damage of endothelial barrier permselectivity could be involved in acute and late delayed toxic effects of intrathecal methotrexate and of CNS irradiation.
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PMID:Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation. 385 68


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