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)

Acute lymphatic leukemia (ALL) represents one of the most frequent malignancies in childhood. Central venous access ports or partly implanted silicone catheters are usually placed for high-dose chemotherapy in these children. We report two patients aged 7 and 3 years with acute lymphoblastic beta-cell leukemia (B-ALL), a less common subtype of ALL, which presented with hyperthermia (38.4 degrees C and 39 degrees C) during anesthesia with isoflurane for implantation of a central venous catheter. The hyperthermic reactions were accompanied by an increase in expired CO2 and acidosis as well as moderate elevation of heart rate and blood pressure. As in both patients the history and preoperative findings did not reveal signs of infection or other causes of fever, the observed alterations were interpreted as symptoms of malignant hyperthermia triggered either by succinylcholine or isoflurane, which were used in both children. In addition, the hyperthermia responded to administration of dantrolene sodium according to dose recommendations for treatment of malignant hyperthermia. In one of the patients, withdrawal of dantrolene during the initial postoperative hours was followed by a recurrent increase in body temperature, which once again could be suppressed by additional dantrolene infusion. According to the literature, malignant hyperthermia has occasionally been described in children with malignancies such as leukemia or Burkitt's lymphoma. Our observations indicate that children with B-ALL may be especially susceptible to malignant hyperthermia. Close monitoring of body temperature and expiratory CO2 are therefore indicated in these children, and dantrolene therapy should be started immediately in case of increased temperature during anesthesia.
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PMID:[Hyperthermic reaction in the perioperative phase in 2 children with acute lymphoblastic leukemia of B-cell type]. 292 70

Proliferation and differentiation are inversely related in many cell culture systems. The study of inducible systems is facilitated by optimal growth conditions in order that whatever differentiation is observed may be attributed to a specific effect of the inducer, rather than to a nonspecific effect of adverse growth conditions. To investigate the role of CO2 supply in an inducible system, the K562 human leukemia cell line inducible for hemoglobin synthesis was studied at 10%, 5% and 1.5% CO2 concentrations. The lower the CO2 concentration, the higher the percentage of benzidine-positive cells but the slower the growth rate. This increase in benzidine positivity reflected hemoglobin synthesis as indicated by incorporation of 3H-leucine into globin chains. If, in addition to reducing CO2 concentration, the complete medium was replaced by a bicarbonate-free medium, the percentage of benzidine-positive cells was further increased and growth further slowed. However, if endogenously produced CO2 was retained by sealing the culture vessel, these effects were mitigated. Since addition of ribosides blocked these effects, the mechanism for these effects appears to be inhibition of riboside biosynthesis due to the depletion of CO2 as a substrate. The implication of this work is that, for reproducibility in studies of inducible systems in which reduction of proliferation may itself increase the probability of differentiation, the CO2 tension, the bicarbonate concentration in the medium and the rate of egress of endogenously produced CO2 must be kept constant.
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PMID:Induction of hemoglobin synthesis in K562 cells by carbon dioxide deficiency. 310 85

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
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PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32

The neutropenia occurring during infection is a poorly understood phenomenon. Immunologically-stimulated T lymphocytes, acting upon normal bone marrow stem cells, have been etiologically implicated in several disorders. Fifteen patients, ages 17 to 25 years, and diagnosed with infectious mononucleosis by positive heterophile titers, were studied. Peripheral blood T lymphocytes were separated using sheep red blood cell rosetting. They were then cocultured with normal bone marrow cells, in a concentration of 2 X 10(4) cells/ml, in methylcellulose containing 10% colony-stimulating activity. Normal BM was obtained from patients with nonmalignant hematologic disorders, or leukemia in remission. Bone marrow cells were cultured at a concentration of 1 X 10(5) or 5 X 10(5) cells/ml, alone (control) or with T lymphocytes. Plates were incubated at 37 degrees C with 5% CO2. Colonies were scored at 14 days. Inhibition of normal, bone marrow growth was observed at both concentrations, after addition of T lymphocytes to the culture system. Such suppression was significant (p less than 0.05) for the lower concentration of normal bone marrow cells only. Variable and partial abrogation of effect was seen after overnight incubation of T lymphocytes, possibly due to loss of suppressor activity. There were insufficient numbers of tests with supernatant to allow computation of statistical significance. Correlation between T-cell ratios and suppressive effect has not been determined, although it is suspected that the responsible cells are within the T-suppressor fraction.
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PMID:The effect of T cells from patients with infectious mononucleosis on CFU-CGM proliferation: a preliminary report. 348 24

Bone marrow blood flow has been assessed using positron emission tomography and the 15O-labelled carbon dioxide steady-state technique. The measurements were performed at the site of the posterior iliac crest. The bone marrow blood flow was 10.0 ml/min/100 cm3 +/- 3.0 (SD) in normal volunteers. It was markedly increased in patients with polycythaemia vera (26.9 +/- 4.6), chronic granulocytic leukaemia (25.2 +/- 3.9) and myelofibrosis (35.1 +/- 7.3). However, bone marrow blood flow did not differ from normal in patients with aplastic anaemia, chronic haemolysis or chronic lymphocytic leukaemia. There was no relationship between bone marrow cellularity and bone marrow blood flow. The data show that bone marrow blood flow is markedly elevated in polycythaemia vera, myelofibrosis and chronic granulocytic leukaemia and suggest that bone marrow cellularity is not a major factor in regulating bone marrow blood flow.
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PMID:Assessment of bone marrow blood flow using positron emission tomography: no relationship with bone marrow cellularity. 349 64

The antitumor activity and mode of action of antitumor agents were assayed by a new method which takes a relatively short time for evaluation. The method was clinically applied to patients with malignant lymphoma or acute leukemia for estimating drug sensitivity. Fresh malignant cells were obtained from patients' bone marrow, lymph nodes, or peripheral blood using Lymphoprep methods in 26 patients with these malignant disorders. Each sample (5 X 10(5) cells/ml) was cultured in the medium with RPMI 1640 supplemented with 10% of FCS and 20% of patients' own sera containing every antitumor agent at predetermined concentrations for 30 minutes. Each sample was again cultured for another 72 hours at 37 degrees C in a 5% CO2 humidified atmosphere after rinsing. Microscopic observation was periodically carried out using a specially devised observation chamber with an inverted immersion microscope for 72 hours. Morphological changes of 200 to 300 cells of each sample were described according to morphological criteria. Of these, irreversible changes in number were considered to be indicative of antitumor activity of the agent tested. More than 50% cellular damage was categorized as effective and more than to 50% reduction of leukemia cells or decrease in size of lymph nodes the same degree in malignant lymphoma were considered to be clinically effective. Forty-four assay runs in 26 patients were done, and on 31 occasions were shown to be coincident. We conclude that this in vitro method is fully applicable for predicting the effectiveness of an agent to be clinically administered regardless of the various controversial problems to be solved.
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PMID:[In vitro predictive activity assay of agents based on dynamic cellular morphological findings--clinical application]. 372 38

A total of 263 primary non-small cell lung cancer patients resected in our Institute from March, 1978 to October, 1984 were utilized in order to evaluate the efficacy of transfer factor (TF) immunotherapy as an adjunct to surgical treatment and TF was significantly effective to cases with stage I diseases, but not to stages II, III and IV diseases, indicating that TF could only suppressed micrometastasis existing at the time of surgery. In order to improve the further results of immunotherapy as an adjunct to surgical treatment, we analyzed cytotoxic activity against autologous lung cancer and K562 leukemia cells in tumor bearing hosts. Furthermore, we studied the effect of interleukin 2 (IL2) activated lymphocyte dialysate on cytotoxic activity against lung cancer cells. When 3 different sources of lymphocytes including peripheral blood lymphocytes (PBL) regional lymphnode cells (LNC) and tumor infiltrating lymphocytes (TIL) were incubated with IL2 for 8 days at 37 degrees C in 5% CO2 atmosphere, relatively high cytotoxic activity was demonstrated with 2 major different patterns in PBL, LNC and TIL including one systemic predominant and the other local predominant patterns, suggesting that IL2 might be a local or systemic possible immunotherapeutic reagent. Finally, we stimulated lymphocytes from household contact family members with IL2 and MMC treated lung cancer cells. These in vitro modulated T-lymphocytes demonstrated considerable cytotoxic activity against the target cells which were used as in vitro sensitization. The dialysate of these in vitro stimulated cells showed specific activity on cytotoxicity against lung cancer cells and might be a possible reagent in stead of TF for clinical trial.
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PMID:[The results of immunotherapy as an adjunct to the surgical treatment of primary lung cancers]. 387 37

Mice that had received 10(6) P388 leukemia cells IV 8 days previously exhibited a decrease in the components of the hepatic microsomal mixed function oxidase, with a 58% decrease in cytochrome P-450, and up to a 60% decrease in hepatic microsomal metabolism of biphenyl. Liver weight was increased by 49% due to infiltration of the liver with leukemic cells. Changes in liver drug-metabolizing activity and liver weight were not seen 6 days after administration of P388 leukemia. There was a small increase in serum liver enzyme but no increase in total serum bilirubin in tumor-bearing mice. In vivo total-body plasma clearance of cyclophosphamide, a drug metabolized by hepatic cytochrome P-450, was decreased to 53 ml/min/kg in mice that had received P388 cells 8 days earlier, as against 97.2 ml/min/kg in control mice. Cytochrome P-450-independent metabolism of [14C]5-fluorouracil, measured by means of [14C]CO2 in the breath over 3 h, was decreased to 21% of the dose administered by 8 days after tumor cell administration, compared with 31% of the dose in control mice. P388 leukemia cells growing in the ascitic form in the intraperitoneal cavity of mice did not release an inhibitor of 5-fluorouracil metabolism into the ascitic fluid. Total-body plasma clearance of indocyanine green was decreased to 11 ml/min/kg by 8 days after P388 cell administration, compared with 36 ml/min/kg in control mice. The decrease in indocyanine green clearance might reflect a decrease in hepatic blood flow in the tumor-bearing mice. A possible explanation for the decrease in hepatic drug metabolism caused by P388 leukemia is that the hepatocytes are deprived of oxygen and nutrients by the tumor in the liver, coupled with or caused by a physical obstruction of hepatic blood flow.
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PMID:Effects of advanced leukemia on hepatic drug-metabolizing activity in the mouse. 394 Feb 19

Infection in vitro of freshly explanted N:NIH(S) mouse bone marrow with ectopic murine leukemia viruses produced an increase over control uninfected cultures in the 50 or more cell granulocyte-macrophage (GM) colonies and 10-49 cell clusters detected after 7 days of incubation in 0.3% agar at 37 degrees C and 7% CO2. This effect was observed only at plating densities above 5.0 X 10(4) cells/ml and was not observed with macrophage-depleted populations of colony-forming units of GM progenitor cells (GM-CFUc) purified by isopyknic density gradient centrifugation of nonadherent cells harvested from long-term bone marrow cultures. Fewer virus-infected, compared to uninfected, peritoneal exudate macrophages were required to stimulate the same number of GM colonies and clusters in a given number of purified GM-CFUc. In contrast, murine leukemia virus infection of T-lymphocytes or NIH/3T3 embryo fibroblasts did not stimulate release of GM-CFUc coloney-stimulating factor (CSF). Single Cell suspensions of virus-infected freshly explanted whole bone marrow grown in CSF concentrated from L929 or WEHI-3 cell-conditioned medium produced more GM-CFUc colonies and GM clusters/1 X 10(5) cells compared to single cell suspensions of uninfected marrow. This phenomenon suggests that the colonoy-forming cells responding to CSF from virus-infected marrow may have been different from those responding to L929 or WEHI-3 cell CSF. The data indicate that increased granulopoiesis observed following retrovirus infection in vivo or in long-term marrow cultures was attributable in part to virus stimulation of production of CSF by adherent marrow stromal cells including macrophages.
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PMID:Murine leukemia viruses: induction of macrophage production of granulocyte-macrophage colony-stimulating factor in vitro. 625 64

Glutamic acid decarboxylase (GAD) activity in cerebrospinal fluid (CSF) was determined in 53 patients with neurological diseases as follows: Epilepsy (n:17), febrile convulsions (n:3), meningoencephalitis (n:17), encephalopathies (n:10), CNS leukemia (n:3), congenital hydrocephalus (n:2) and pseudoileus neonatorum (n:1). Compared with the mean normal value (5.2 +/- 2.5 pmol CO2 formed/hr/ml) reported in Part I, a significant increase of GAD activity in CSF was demonstrated in patients with uncontrolled epileptic seizures (11.4 +/- 3.9 pmol CO2 formed/hr/ml), febrile convulsions (13.5 +/- 8.7), viral meningitis with or without encephalitis (20.3 +/- 13.6), encephalopathies (30.0 +/- 25.9), CNS leukemia (11.1 +/- 5.0), congenital hydrocephalus (20.5 +/- 7.3) and pseudoileus neonatorum (28.6). Markedly high GAD activity was found in patients with CNS leukemia several days after intrathecal injection of methotrexate (39.8 +/- 18.0). On the other hand, significantly low GAD activity was shown in patients with bacterial meningitis or brain abscess (1.3 +/- 1.2). This suggests that some bacterial factors may be inhibitory toward GAD activity in CSF. High GAD activity in CSF may be useful as an indicator of aseptic brain dysfunction, although it was not always correlated with the severity of symptoms.
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PMID:Glutamic acid decarboxylase in cerebrospinal fluid in infancy and childhood Part II. Glutamic acid decarboxylase activity in cerebrospinal fluid of children with neurological diseases. 666 Apr 21


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